JXB Advance Access published online on October 20, 2007
Journal of Experimental Botany, doi:10.1093/jxb/erm226
REVIEW ARTICLE |
Signalling through kinase-defective domains: the prevalence of atypical receptor-like kinases in plants
Departament de Genètica Molecular Vegetal, Laboratori de Genètica Molecular Vegetal, CSIC-IRTA, Jordi Girona 18, Barcelona, Spain
* To whom correspondence should be addressed. E-mail: jcsgmp{at}cid.csic.es
Received 12 June 2007; Revised 1 August 2007 Accepted 28 August 2007
 |
Abstract |
|---|
 Top Abstract Receptor protein kinases and...Atypical receptor kinases:...Prevalence of atypical RLKsSupplementary materialReferences |
|---|
The structure of plant receptor-like kinases (RLKs) is similar to that of animal receptor tyrosine kinases (RTKs), and consists of an extracellular domain, a transmembrane span, and a cytoplasmic domain containing the conserved kinase domain. The mechanism by which animal RTKs, and probably plant RLKs, signal includes the dimerization of the receptor, their intermolecular phosphorylation, and the phosphorylation of downstream signalling proteins. However, atypical RTKs with a kinase-dead domain that signal through phosphorylation-independent mechanisms have also been described in animals. In the last few years, some atypical RLKs have also been reported in plants. Here these examples and their possible signalling mechanisms are reviewed. Plant genomes contain a much larger number of genes coding for receptor kinases than other organisms. The prevalence of atypical RLKs in plants is analysed here. A sequence analysis of the Arabidopsis kinome revealed that 13% of the kinase genes do not retain some of the residues that are considered as invariant within kinase catalytic domains, and are thus putatively kinase-defective. This percentage rises to close to 20% when analysing RLKs, suggesting that phosphorylation-independent mechanisms mediated by atypical RLKs are particularly important for signal transduction in plants.
Key words: Atypical kinases, phosphorylation, RLK, signalling
|
Receptor protein kinases and signal transduction: the importance of phosphorylation |
|---|
|
TopAbstractReceptor protein kinases and...Atypical receptor kinases:...Prevalence of atypical RLKsSupplementary materialReferences |
|---|
All living organisms receive and process information at the cellular level through various classes of receptors, which recognize signals from the environment or from neighbouring cells and activate downstream signalling cascades. A particular type of receptors are receptor kinases (RKs), which are found in metazoans and plants. RKs are characterized by the presence of an extracellular domain, which specifically recognizes the ligand, linked by a transmembrane region to a cytoplasmic kinase domain.
RK activation has been extensively studied in animals, where it has been shown to be a phosphorylation-dependent mechanism which generally involves two steps: first, ligand binding and receptor oligomerization resulting in the intracellular kinase domain activation; and secondly, upon activation, intermolecular autophosphorylation and conformational changes allowing the receptor to bind and activate downstream signalling proteins (Pawson and Nash, 2000). Two classes of RKs are found in animals, the receptor tyrosine kinases (RTKs) and the serine/threonine kinase receptors (STRKs). The best known example of STRK is the transforming growth factor (TGF)–ß receptor complex, which is formed by a heteromeric complex of two different receptors. The type II receptor (also known as the primary receptor) binds the ligand and this triggers the phosphorylation of the type I receptor (also known as the transducer), which cannot bind the ligand in the absence of type II receptors. Phosphorylation of the transducer allows further signalling to downstream cascades (Massagué, 1996). The second class of animal RKs, the RTKs, act as ligand-activated homodimers or heterodimers of two related RTKs. Autophosphorylation in the activation loop of the kinase domain results in stimulation of the kinase activity. This allows its subsequent tyrosine phosphorylation that generates docking sites to recruit downstream signalling components, which may also be activated by phosphorylation triggering signalling cascades (Ulrich and Schlessinger, 1990; Hubbard and Till, 2000).
The structure of plant receptor-like kinases (RLKs) is similar to that of animal RKs, being composed of an extracellular domain, a transmembrane span, and a cytoplasmic domain containing the conserved kinase domain. Nevertheless, in contrast to animal RKs, which in most cases are tyrosine kinases, all reported plant RLKs have serine/threonine kinase specificity.
Different studies suggest that the mechanism of activation of plant RLKs may be similar to the mechanism of activation of animal RTKs (Shiu and Bleecker, 2001a; Cock et al., 2002; Morris and Walker, 2003; Johnson and Ingram, 2005). RLK autophosphorylation seems to be a common step in plants since a large number of RLKs have been described to autophosphorylate. For some of them, experimental evidence suggests that autophosphorylation is particularly important for their function. For instance, the Brasssica SRK, the self-incompatibility receptor, is autophosphorylated only when pollinated with incompatible pollen (Cabrillac et al., 2001). On the other hand, biochemical analyses revealed that the intracellular domain of the resistance protein Xa21 is autophosphorylated in Ser686, Thr688, and Ser689 (Xu et al., 2006), and the substitution of these residues by an alanine destabilizes the protein and compromises Xa21-mediated pathogen resistance (Xu et al., 2006). The activation of the Brassinosteroid receptor (BRI1) is one of the best characterized mechanisms of RLK activation in plants (Belkhadir and Chory, 2006). It has been demonstrated that BRI1 binds the brassinolide (Kinoshita et al., 2005) and that brassinolide treatment results in BRI1 autophosphorylation and activation (Wang et al., 2005a). In the absence of its ligand, BRI1 is inhibited by its C-terminal tail (Wang et al., 2005b) and by BRI1 kinase inhibitor 1 (BKI1) (Wang and Chory, 2006). This inhibition is released upon binding of the brassinolide to the BRI1 oligomer and consequent autophosphorylation of the activation loop of the receptor (Wang and Chory, 2006), and the subsequent phosphorylation allows the formation of the putative active complex BRI1–BAK1 (Wang et al., 2005a).
On the other hand, the analysis of mutants of two receptors, CLV1, which is involved in apical meristem development, and FLS2, involved in pathogen-triggered defence responses, suggested that kinase activity may also be required for ligand binding. Indeed, mutated constructs of CLV1 and FLS2 lacking kinase activity do not interact with CLV3 or flagellin, their respective ligands (Trotochaud et al., 1999; Gómez-Gómez and Boller, 2000).
Furthermore, kinase activity seems to be essential for RLK signal transduction since severe phenotypes are obtained when introducing mutations that disrupt kinase activity in BRI1 (Friedrichsen et al., 2000), CLV1 (Clark et al., 1997), FLS2 (Gómez-Gómez et al., 2001), SRK (Stahl et al., 1998), and also in ERECTA, an RLK regulating organ formation (Lease et al., 2001; Shpack et al., 2003), and SYMRK/NORK, RLKs that participate in nodulation (Stracke et al., 2002).
These observations indicate that kinase activity is required at different steps of RLK activation and suggest that RLK signal transduction is a phosphorylation-dependent mechanism in plants, as has been shown in animal systems.
|
Atypical receptor kinases: transduction without phosphorylation |
|---|
|
TopAbstractReceptor protein kinases and...Atypical receptor kinases:...Prevalence of atypical RLKsSupplementary materialReferences |
|---|
While, as reviewed above, the general RK activation mechanism is phosphorylation-dependent, kinase-defective atypical RKs transducing signals by phosphorylation-independent mechanisms have also been described in animals and very recently in plants.
Catalytic kinase domains consist of 250–300 residues subdivided into 12 conserved subdomains (Hanks et al., 1988). The domain forms a two-lobed structure joined by subdomain V. The small N-terminal lobe (i.e. subdomains I–IV) participates in anchoring and orienting the ATP molecule, while the large C-terminal lobe (i.e. subdomains VIa–XI) binds the protein substrate and initiates the phosphotransfer. Each of the 12 subdomains contains conserved residues thought to be essential for the catalytic activity (Hanks and Hunter, 1995). This is the case for the aspartic acid of subdomain VIb which is part of the kinase active site (Knighton et al., 1993; Taylor et al., 1995), or the DFG motif of subdomain VII, involved in cation binding and orientation of the ATP gamma phosphate for phosphate transfer (Knighton et al., 1993; Hanks and Hunter, 1995; Huse and Kuriyan, 2002). Several atypical RKs that do not present some of the conserved residues of their kinase domains have been described in animals. These proteins include the human CCK-4 (Mossie et al., 1995), H-Ryk (Hovens et al., 1992; Katso et al., 1999), and ErbB-3 (Guy et al., 1994; Sierke et al., 1997), and the Drosophila DNT proteins (Savant-Bhonsale et al., 1999).
The ErbB3 receptor belongs to the EGFR family of RTKs, which includes ErbB1/EGF, ErbB2/neu/HER2, ErbB3, and ErbB4 (Stein and Staros, 2000). The ErbB3 sequence contains substitutions of some of the highly conserved residues within the kinase-like domain, particularly the aspartic acid of subdomain VIb, and it has been demonstrated that its kinase activity is significantly impaired (Kim et al., 1998). In spite of this fact, ErbB3 is essential for proper signalling since mouse ErbB3 knockouts are lethal at embryonic stages (Riethmacher et al., 1997). ErbB3 forms heterodimers with other members of the EGFR family that phosphorylate it (Kim et al., 1998). Phosphorylated residues of the intracellular domain of ErbB3 act as docking sites, allowing the interaction with downstream signalling proteins, including phosphatidylinositol 3-kinase and SHC (Prigent et al., 1994), which are effector proteins responsible for mitogen-activated protein kinase (MAPK) cascade activation (Citri et al., 2003) (Fig. 1). The human CCK-4 RTK (Mossie et al., 1995) and its orthologous proteins, the chicken Klg (Chou and Hayman, 1991), the hydra Lemon (Miller and Steele, 2000), and the Drosophila Drtk (Pulido et al., 1992), also contain substitutions of some of the highly conserved residues within the kinase-like domain. In particular these proteins do not present the DFG motif of subdomain VII and also lack kinase activity. Their mechanism of activation is unknown, but the fact that their sequences contain elements that could mediate protein–protein interactions suggests that CCK-4 members may interact with kinase-active partners and signal in a way similar to that of the human ErbB3 atypical RTK.
|
On the other hand, members of the Ryk family in Caenorhabditis elegans (Halford et al., 1999), Drosophila (Savant-Bhonsale et al., 1999), and vertebrates (Hovens et al., 1992) also contain substitutions of the DFG motif, and also lack kinase activity (Katso et al., 1999). H-Ryk also forms heterodimers with other kinase-active RTKs, although in this case the interaction does not result in phosphorylation of the inactive kinase (Trivier and Ganesan, 2002). A chimeric receptor approach showed that the ligand stimulation of H-Ryk results in the activation of a MAPK pathway (Katso et al., 1999), suggesting that the activated H-Ryk can interact with and activate other downstream signalling proteins.
Catalytically impaired kinases belonging to classes other than RKs have also been reported. Those atypical kinases, which are also essential for signal transduction, are proposed to function as scaffolds or docking platforms. The kinase suppressor of Ras (KSR) lacks the conserved lysine in the ATP-binding domain (Therrien et al., 1995), and biochemical experiments suggested that it does not exhibit kinase activity. More importantly, it has been reported that KSR constructs containing mutations which usually disrupt kinase activity rescued the KSR loss-of-function phenotype. This observation indicates that KSR mutants can be restored by a kinase-independent mechanism (Stewart et al., 1999). It is suggested that KSR acts as a scaffolding protein (Morrison, 2001) that interacts with Raf, MEK, and ERK, and co-ordinates their membrane localization, facilitating mitogen-activated kinase activation (Ritt et al., 2005). Similarly, kinase-impaired constructs of integrin-like kinase (ILK), which is essential for integrin-mediated adhesion of muscles in C. elegans and Drosophila, can rescue null mutations of ILK (Zervas et al., 2001). This points to a phosphorylation-independent role for ILK and it has been suggested that the ILK kinase domain might function as a platform for protein–protein interactions (Zervas and Brown, 2002).
In summary, atypical RKs signal through phosphorylation-independent mechanisms involving regulated protein–protein interactions mediated by their intracellular kinase-like domains (Kroiher et al., 2001). The importance of protein–protein interactions for signalling through these proteins probably explains why all these atypical RKs have maintained during evolution the general structure of their kinase domains in spite of their lack of kinase activity (Stein and Staros, 2000).
In the last few years, atypical plant RLKs that could transduce signals by phosphorylation-independent mechanisms have also been described in plants (Llompart et al., 2003; Cao et al., 2005; Chevalier et al., 2005).
MARK (maize atypical receptor kinase) contains alterations of some conserved amino acids within the kinase domain (Llompart et al., 2003) (Fig. 2). The MARK sequence lacks the conserved aspartic acid of subdomain VIb, and the aspartic acid and phenylalanine within the DFG motif of subdomain VII. All those alterations suggest that the intracellular domain of MARK could be a kinase-dead domain. Moreover, recombinant MARK fails to auto- and transphosphorylate in vitro (Llompart et al., 2003). It has been demonstrated that the intracellular domain of MARK interacts with the C-terminal domain of a maize GCK-like kinase named MIK, and this interaction results in the activation of MIK kinase activity (Llompart et al., 2003). As the C-terminal domain of MIK inhibits its own kinase activity (Castells et al., 2006), MARK probably activates MIK by inducing conformational changes that release MIK autoinhibition (Castells et al., 2006) (Fig. 1C). Those findings showed for the first time in plants that atypical RLKs can transduce signals by means of phosphorylation-independent mechanisms. Another putative kinase-dead RLK, the Arabidopsis TMKL1 protein, had been described earlier (Valon et al., 1993) but its kinase activity has not been analysed. The sequence of TMKL1 contains alterations of several conserved residues within the kinase domain: in particular, the glycine-rich domain of subdomain I, the invariant lysine of subdomain II, the invariant glutamic acid of subdomain II, the aspartic acid of subdomain VIb, and the aspartic acid of subdomain VII (Fig. 2), suggesting that TMKL1 may be an atypical RLK with a kinase-dead domain.
|
Recently, the analysis of two additional atypical RLKs has been reported. The Arabidopsis Strubbelig (SUB) RLK plays an essential role in Arabidopsis organ development, since sub mutants show defects in ovule development. SUB contains a kinase domain containing two substitutions of conserved amino acids within the catalytic loop (Fig. 2). The conserved aspartic acid of subdomain VIb is substituted by an asparagine, and the conserved asparagine of the same domain by a lysine. Biochemical approaches demonstrated that SUB lacks kinase activity, and, remarkably, genetic experiments showed that the catalytic activity is not essential for in vivo SUB function (Chevalier et al., 2005). Nothing is known on the possible signalling mechanism of SUB, but it has been suggested that its kinase-dead domain could have maintained the ability to interact with downstream effectors requiring the typical three-dimensional configuration of a kinase domain (Chevalier et al., 2005).
The second reported analysis on atypical RLKs refers to the Arabidopsis ATCRR1 and ATCRR2 receptors, both related to the maize CRINKLY4 receptor which is implicated in maize development. Arabidopsis ATCRR1 and ATCRR2 have a deletion of subdomain VIII (Fig. 2) and display significantly attenuated kinase activity in vitro. It has been shown that ATCRR2 can be phosphorylated by ACR4, the Arabidopsis CRINKLY4 homologue, in vitro, suggesting that these proteins could signal through ATCRR2–ACR4 heterodimerization and subsequent transphosphorylation of ATCRR2, a mechanism reminiscent of that of the human ErbB3 RTK (Cao et al., 2005). Interestingly, a recent report shows that, although ACR4 is an RLK with an active kinase domain, its kinase activity may not be required for protein function (Gifford et al., 2005). Indeed, an ACR4 kinase-dead mutant can complement the acr4 mutant phenotype, suggesting that at least part of ACR4 signalling may pass via a route independent of its kinase activity (Gifford et al, 2005).
|
Prevalence of atypical RLKs |
|---|
|
TopAbstractReceptor protein kinases and...Atypical receptor kinases:...Prevalence of atypical RLKsSupplementary materialReferences |
|---|
The human genome contains 518 genes coding for protein kinases (Manning et al., 2002). An analysis of the human kinome revealed that 50 human kinase domains lack the conserved lysine of subdomain II, the aspartic acid of subdomain VIb, or the aspartic acid of subdomain VII, suggesting that 10% of the predicted human kinase proteins are putatively enzymatically inactive (Manning et al., 2002) (Table 1). The mouse kinome shows an almost perfect conservation of the predicted inactive kinases (Caenepeel et al., 2004), suggesting that most of these proteins fulfil a cellular role and that their corresponding genes are not merely pseudogenes.
|
A general survey of 911 sequences of the Arabidopsis kinome has been performed and it was found that 13% of the putative kinases lack the conserved lysine of subdomain II, the aspartic acid of subdomain VIb, or the aspartic acid of subdomain VII, and are putatively enzymatically inactive (Table 1). This percentage is slightly higher than that found in mammals, although both plants and mammals have a higher percentage of putative defective kinases than yeast, where only six out of the 94 kinase-encoding genes analysed lack those conserved residues (Table 1). Intriguingly, when analysing the RLK/Pelle family, which include the RLKs and the receptor-like cytoplasmic kinases, or RLCKs, this percentage rises to 20% (Table 1). A detailed sequence analysis of the Arabidopsis RLK/Pelle family members was performed and it was found that 121 out of the 610 analysed sequences lack the conserved aspartic acid of subdomain VIb or the DFG motif of subdomain VII. More precisely, 77 sequences lack the aspartic acid of subdomain VIb, 17 lack the DFG motif of subdomain VII, and 27 lack both motifs. These proteins are predicted to be defective kinases, as all these mutations have been reported to disrupt the kinase catalytic activity.
Plant genomes contain a much larger number of genes coding for protein kinases than mammalian genomes (Champion et al., 2004; Krupa et al., 2004). For instance, the Arabidopsis genome comprises 
1000 genes coding for kinases (Champion et al., 2004), and the RLK/Pelle gene family, with some 600 genes (Shiu and Bleeker, 2001b), is one of the largest gene families in Arabidopsis and in the plant kingdom in general. Different hypotheses have been formulated to explain the high number of plant RLKs, and plant kinases in general, compared with animals. Plants, as sessile organisms, may perceive and integrate more signals to adapt their morphogenesis to the changing environment. Alternatively, the mechanisms of signalling may have diverged between plants and animals and, as a consequence, plants might need a larger number of receptors. Finally, the low frequency of alternative splicing leading to different isoforms from a single gene in plants compared with animals (Ner-Gaon et al., 2004) could be compensated by an increase in the number of kinase genes. It has been suggested that tandem duplications and segmental/whole-genome duplications are the major mechanisms for the expansion of the RLK family in Arabidopsis (Shiu and Bleecker, 2003). The high expansion of the RLK gene family through gene duplication could have allowed the maintenance of mutations affecting kinase activity and the subsequent evolution of new functions for these atypical RLKs, which could explain the particular prevalence of defective kinases within plant RLKs.
Most atypical RLKs belong to a few of the previously defined subfamilies of the RLK/Pelle family (Shiu and Bleecker, 2001b), the subfamilies LRRIII, LRRIV, LRRV, LRRVI, LRRVII, RLCKI, RLCKII, and RLCKIII. In some of these subfamilies, most of the sequences lack the aspartic acid of subdomain VIb. For instance, eight out of the nine members of the LRRV subfamily lack the aspartic acid of subdomain VIb (shown in red in Fig. 3). A phylogenetic analysis by Neighbor–Joining and maximum-likelihood approaches suggests that the aspartate loss may have occurred after At5g06820 gene duplication, the mutated gene giving rise to eight new members with the same mutation (Fig. 3). A mutation in a single sequence whose amplification has given rise to the whole subfamily is also one of the most parsimonious hypotheses for the formation of the LRRIV subfamily, where all the sequences contain the same inactivating mutation (see Supplementary Fig. S1A, B at JXB online). In other cases, the phylogenetic relationships of the different mutated genes suggest that some atypical members may have experienced a second mutation restoring the conserved amino acid. This is probably the case for the LRRIII subfamily, where most proteins have the aspartate mutation to arginine in subdomain VIb while five of them (shown in black in Fig. 4) have the conserved aspartate, and this is probably also the case for the group formed by the LRRVI and RLCKI subfamilies where two sequences do not present this inactivating mutation (see Supplementary Fig. S1C, D at JXB online). On the other hand, most of the subfamilies also contain sequences that have an additional substitution in the DGF motif of subdomain VII. This is the case for the LRRIII (Fig. 4), LRRIV (see Supplementary Fig. S1A, B at JXB online), and LRRVI (see Supplementary Fig. S1C, D at JXB online) subfamilies where the phylogenetic analysis is compatible with mutations of subdomain VII occurring in some already inactivated proteins. This could indicate that after a kinase-inactivating substitution the selective pressure to maintain invariable the amino acids important for kinase activity diminishes, and a second inactivating mutation is more frequently allowed. On the other hand, the mutation of subdomain VII could also arise in some cases independently or even prior to the mutation in subdomain VIb, as could be suggested to explain the phylogenetic relationships of the proteins of the LRRVII, RLCKII, and RLCKIII subfamilies (see Supplementary Fig. S1E, F; G, H; and I, J at JXB online). In the case of RLCKII, both the Neighbor–Joining and the maximum-likelihood analyses suggest that the mutation of the DFG motif of subdomain VII may have occurred in the ancestor of the group, while two independent mutations of the aspartate of subdomain VIb occurred later in evolution to give rise to the sequences having mutations in both subdomains.
|
|
Thus, the phylogenetic analysis of the LRR subfamilies containing atypical receptor kinases suggests that atypical RLKs had arisen independently multiple times and, more importantly, that different atypical RLKs had been maintained and expanded through evolution. Moreover, the phylogenetic analysis of RLKs, already published by Shiu and Bleecker (2001b), shows that the eight subgroups that contain atypical RLKs and that have been analysed here are not phylogenetically related, reinforcing the idea that the mutations of the atypical RLKs do not have a monophyletic origin.
In summary, close to 20% of Arabidopsis RLKs present substitutions in highly conserved amino acids within the kinase domain, being putative atypical kinase receptors. This observation suggests that phosphorylation-independent mechanisms mediated by atypical RLKs are important in signal transduction in plants, as they have been shown to be in animal systems.
|
Supplementary material |
|---|
|
TopAbstractReceptor protein kinases and...Atypical receptor kinases:...Prevalence of atypical RLKsSupplementary materialReferences |
|---|
The phylogenetic analysis of the RLK subfamilies LRRIV, LRRVI and LRCKI, LRRVII, LRCKII, and LRCKIII are presented in Supplementary Fig. S1A, B; C, D; E, F; G, H; and I, J, respectively, available at JXB online.
|
Acknowledgements |
|---|
We are grateful to Paloma Mas, Soraya Pelaz, and Jaume Martínez-García for their critical reading of the manuscript, and to José Castresana for his help with the phylogenetic analysis. This work was partially funded by Centre de Referència en Biotecnologia (CeRBa) from the Generalitat de Catalunya.
|
References |
|---|
|
TopAbstractReceptor protein kinases and...Atypical receptor kinases:...Prevalence of atypical RLKsSupplementary materialReferences |
|---|
Belkhadir Y, Chory J. Brassinosteroid signaling: a paradigm for steroid hormone signaling from the cell surface. Science (2006) 314:1410–1411.
Cabrillac D, Cock JM, Dumas C, Gaude T. The S-locus receptor kinase is inhibited by thioredoxins and activated by pollen coat proteins. Nature (2001) 410:220–223.[CrossRef][Medline]
Caenepeel S, Charydczak G, Sudarsanam S, Hunter T, Manning G. The mouse kinome: discovery and comparative genomics of all mouse protein kinases. Proceedings of the National Academy of Sciences, USA (2004) 101:11707–11712.
Cao X, Li K, Suh SG, Guo T, Becraft PW. Molecular analysis of the CRINKLY4 gene family in Arabidopsis thaliana. Planta (2005) 220:645–657.[CrossRef][Web of Science][Medline]
Castells E, Puigdomenech P, Casacuberta JM. Regulation of the kinase activity of the MIK GCK-like MAP4K by alternative splicing. Plant Molecular Biology (2006) 61:747–756.[CrossRef][Web of Science][Medline]
Champion A, Kreis M, Mockaitis K, Picaud A, Henry Y. Arabidopsis kinome: after the casting. Functional and Integrative Genomics (2004) 4:163–187.
Chevalier D, Batoux M, Fulton L, Pfister K, Yadav RK, Schellenberg M, Schneitz K. STRUBBELIG defines a receptor kinase-mediated signaling pathway regulating organ development in Arabidopsis. Proceedings of the National Academy of Sciences, USA (2005) 102:9074–9079.
Chou YH, Hayman MJ. Characterization of a member of the immunoglobulin gene superfamily that possibly represents an additional class of growth factor receptor. Proceedings of the National Academy of Sciences, USA (1991) 88:4897–4901.
Citri A, Skaria KB, Yarden Y. The deaf and the dumb: the biology of ErbB-2 and ErbB-3. Experimental Cell Research (2003) 284:54–65.[CrossRef][Web of Science][Medline]
Clark SE, Williams RW, Meyerowitz EM. The CLAVATA1 gene encodes a putative receptor kinase that controls shoot and floral meristem size in Arabidopsis. Cell (1997) 89:575–585.[CrossRef][Web of Science][Medline]
Cock JM, Vanoosthuyse V, Gaude T. Receptor kinase signaling in plants and animals: distinct molecular systems with mechanistic similarities. Current Opinion in Cell Biology (2002) 14:230–236.[CrossRef][Web of Science][Medline]
Friedrichsen DM, Joazeiro CA, Li J, Hunter T, Chory J. Brassinosteroid-insensitive-1 is a ubiquitously expressed leucine-rich repeat receptor serine/threonine kinase. Plant Physiology (2000) 123:1247–1256.
Gifford ML, Robertson FC, Soares DC, Ingram GC. ARABIDOPSIS CRINKLY4 function, internalization, and turnover are dependent on the extracellular crinkly repeat domain. The Plant Cell (2005) 17:1154–1166.
Gomez-Gomez L, Bauer Z, Boller T. Both the extracellular leucine-rich repeat domain and the kinase activity of FSL2 are required for flagellin binding and signaling in Arabidopsis. The Plant Cell (2001) 13:1155–1163.
Gomez-Gomez L, Boller T. FLS2: an LRR receptor-like kinase involved in the perception of the bacterial elicitor flagellin in Arabidopsis. Molecular Cell (2000) 5:1003–1011.[CrossRef][Web of Science][Medline]
Guindon S, Gascuel O. A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Systematic Biology (2003) 52:696–704.
Guy PM, Platko JV, Cantley LC, Cerione RA, Carraway KL 3rd. Insect cell-expressed p180erbB3 possesses an impaired tyrosine kinase activity. Proceedings of the National Academy of Sciences, USA (1994) 91:132–13.
Halford MM, Oates AC, Hibbs ML, Wilks AF, Stacker SA. Genomic structure and expression of the mouse growth factor receptor related to tyrosine kinases (Ryk). Journal of Biological Chemistry (1999) 274:7379–7390.
Hanks SK, Quinn AM, Hunter T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science (1988) 241:42–52.
Hovens CM, Stacker SA, Andres AC, Harpur AG, Ziemiecki A, Wilks AF. RYK, a receptor tyrosine kinase-related molecule with unusual kinase domain motifs. Proceedings of the National Academy of Sciences, USA (1992) 89:11818–11822.
Hubbard SR, Till JH. Protein tyrosine kinase structure and function. Annual Review of Biochemistry (2000) 69:373–398.[CrossRef][Web of Science][Medline]
Huse M, Kuriyan J. The conformational plasticity of protein kinases. Cell (2002) 109:275–282.[CrossRef][Web of Science][Medline]
Johnson KL, Ingram GC. Sending the right signals: regulating receptor kinase activity. Current Opinion in Plant Biology (2005) 8:648–656.[CrossRef][Web of Science][Medline]
Katso RM, Russell RB, Ganesan TS. Functional analysis of H-Ryk, an atypical member of the receptor tyrosine kinase family. Molecular and Cellular Biology (1999) 19:6427–6440.
Kim HH, Vijapurkar U, Hellyer NJ, Bravo D, Koland JG. Signal transduction by epidermal growth factor and heregulin via the kinase-deficient ErbB3 protein. Biochemical Journal (1998) 334:189–195.[Web of Science][Medline]
Kinoshita T, Cano-Delgado A, Seto H, Hiranuma S, Fujioka S, Yoshida S, Chory J. Binding of brassinosteroids to the extracellular domain of plant receptor kinase BRI1. Nature (2005) 433:167–171.[CrossRef][Medline]
Knighton DR, Cadena DL, Zheng J, Ten Eyck LF, Taylor SS, Sowadski JM, Gill GN. Structural features that specify tyrosine kinase activity deduced from homology modeling of the epidermal growth factor receptor. Proceedings of the National Academy of Sciences, USA (1993) 90:5001–5005.
Kroiher M, Miller MA, Steele RE. Deceiving appearances: signaling by ‘dead’ and ‘fractured’ receptor protein-tyrosine kinases. Bioessays (2001) 23:69–76.[CrossRef][Web of Science][Medline]
Krupa A, Abhinandan KR, Srinivasan N. KinG: a database of protein kinases in genomes. Nucleic Acids Research (2004) 32:D153–D155.
Kumar S, Tamura K, Nei M. MEGA3: integrated software for molecular evolutionary genetics analysis and sequence alignment. Briefings in Bioinformatics (2004) 5:150–163.
Lease KA, Wen J, Li J, Doke JT, Liscum E, Walker JC. A mutant Arabidopsis heterotrimeric G-protein beta subunit affects leaf, flower, and fruit development. The Plant Cell (2001) 13:2631–2641.
Llompart B, Castells E, Rio A, Roca R, Ferrando A, Stiefel V, Puigdomenech P, Casacuberta JM. The direct activation of MIK, a germinal center kinase (GCK)-like kinase, by MARK, a maize atypical receptor kinase, suggests a new mechanism for signaling through kinase-dead receptors. Journal of Biological Chemistry (2003) 278:48105–48111.
Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. The protein kinase complement of the human genome. Science (2002) 298:1912–1934.
Massague J. TGF-beta signal transduction. Annual Review of Biochemistry (1998) 67:753–791.[CrossRef][Web of Science][Medline]
Miller MA, Steele RE. Lemon encodes an unusual receptor protein-tyrosine kinase expressed during gametogenesis in Hydra. Developmental Biology (2000) 224:286–298.[CrossRef][Web of Science][Medline]
Morris ER, Walker JC. Receptor-like protein kinases: the keys to response. Current Opinion in Plant Biology (2003) 6:339–342.[CrossRef][Web of Science][Medline]
Morrison DK. KSR: a MAPK scaffold of the Ras pathway? Journal of Cell Science (2001) 114:1609–1612.[Abstract]
Mossie K, Jallal B, Alves F, Sures I, Plowman GD, Ullrich A. Colon carcinoma kinase-4 defines a new subclass of the receptor tyrosine kinase family. Oncogene (1995) 11:2179–2184.[Web of Science][Medline]
Ner-Gaon H, Halachmi R, Savaldi-Goldstein S, Rubin E, Ophir R, Fluhr R. Intron retention is a major phenomenon in alternative splicing in Arabidopsis. The Plant Journal (2004) 39:877–885.[CrossRef][Web of Science][Medline]
Pawson T, Nash P. Protein–protein interactions define specificity in signal transduction. Genes and Development (2000) 14:1027–1047.
Prigent SA, Gullick WJ. Identification of c-erbB-3 binding sites for phosphatidylinositol 3'-kinase and SHC using an EGF receptor/c-erbB-3 chimera. EMBO Journal (1994) 13:2831–2841.[Web of Science][Medline]
Pulido D, Campuzano S, Koda T, Modolell J, Barbacid M. Dtrk, a Drosophila gene related to the trk family of neurotrophin receptors, encodes a novel class of neural cell adhesion molecule. EMBO Journal (1992) 11:391–404.[Web of Science][Medline]
Riethmacher D, Sonnenberg-Riethmacher E, Brinkmann V, Yamaai T, Lewin GR, Birchmeier C. Severe neuropathies in mice with targeted mutations in the ErbB3 receptor. Nature (1997) 389:725–730.[CrossRef][Medline]
Ritt DA, Daar IO, Morrison DK. KSR regulation of the Raf-MEK-ERK cascade. Methods in Enzymology (2005) 407:224–237.[Web of Science][Medline]
Savant-Bhonsale S, Friese M, McCoon P, Montell DJ. A Drosophila derailed homolog, doughnut, expressed in invaginating cells during embryogenesis. Gene (1999) 231:155–161.[CrossRef][Web of Science][Medline]
Shiu SH, Bleecker AB. Plant receptor-like kinase gene family: diversity, function, and signaling. Sci STKE (2001a) 2001:RE22.[Medline]
Shiu SH, Bleecker AB. Receptor-like kinases from Arabidopsis form a monophyletic gene family related to animal receptor kinases. Proceedings of the National Academy of Sciences, USA (2001b) 98:10763–10768.
Shiu SH, Bleecker AB. Expansion of the receptor-like kinase/Pelle gene family and receptor-like proteins in Arabidopsis. Plant Physiology (2003) 132:530–543.
Shpak ED, Lakeman MB, Torii KU. Dominant-negative receptor uncovers redundancy in the Arabidopsis ERECTA leucine-rich repeat receptor-like kinase signaling pathway that regulates organ shape. The Plant Cell (2003) 15:1095–1110.
Sierke SL, Cheng K, Kim HH, Koland JG. Biochemical characterization of the protein tyrosine kinase homology domain of the ErbB3 (HER3) receptor protein. Biochemical Journal (1997) 322:757–763.[Web of Science][Medline]
Stahl RJ, Arnoldo M, Glavin TL, Goring DR, Rothstein SJ. The self-incompatibility phenotype in brassica is altered by the transformation of a mutant S locus receptor kinase. The Plant Cell (1998) 10:209–218.
Stein RA, Staros JV. Evolutionary analysis of the ErbB receptor and ligand families. Journal of Molecular Evolution (2000) 50:397–412.[Web of Science][Medline]
Stewart S, Sundaram M, Zhang Y, Lee J, Han M, Guan KL. Kinase suppressor of Ras forms a multiprotein signaling complex and modulates MEK localization. Molecular and Cellular Biology (1999) 19:5523–5534.
Stracke S, Kistner C, Yoshida S, et al. A plant receptor-like kinase required for both bacterial and fungal symbiosis. Nature (2002) 417:959–962.[CrossRef][Medline]
Taylor SS, Radzio-Andzelm E, Hunter T. How do protein kinases discriminate between serine/threonine and tyrosine? Structural insights from the insulin receptor protein-tyrosine kinase. FASEB Journal (1995) 9:1255–1266.[Abstract]
Therrien M, Chang HC, Solomon NM, Karim FD, Wassarman DA, Rubin GM. KSR, a novel protein kinase required for RAS signal transduction. Cell (1995) 83:879–888.[CrossRef][Web of Science][Medline]
Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, population-specific gap penalties and weight matrix choice. Nucleic Acids Research (1994) 22:4673–4680.
Trivier E, Ganesan TS. RYK, a catalytically inactive receptor tyrosine kinase, associates with EphB2 and EphB3 but does not interact with AF-6. Journal of Biological Chemistry (2002) 277:23037–23043.
Trotochaud AE, Hao T, Wu G, Yang Z, Clark SE. The CLAVATA1 receptor-like kinase requires CLAVATA3 for its assembly into a signaling complex that includes KAPP and a Rho-related protein. The Plant Cell (1999) 11:393–406.
Ullrich A, Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell (1990) 61:203–212.[CrossRef][Web of Science][Medline]
Valon C, Smalle J, Goodman HM, Giraudat J. Characterization of an Arabidopsis thaliana gene (TMKL1) encoding a putative transmembrane protein with an unusual kinase-like domain. Plant Molecular Biology (1993) 23:415–421.[CrossRef][Web of Science][Medline]
Wang X, Chory J. Brassinosteroids regulate dissociation of BKI1, a negative regulator of BRI1 signaling, from the plasma membrane. Science (2006) 313:1118–11122.
Wang X, Goshe MB, Soderblom EJ, Phinney BS, Kuchar JA, Li J, Asami T, Yoshida S, Huber SC, Clouse SD. Identification and functional analysis of in vivo phosphorylation sites of the Arabidopsis BRASSINOSTEROID-INSENSITIVE1 receptor kinase. The Plant Cell (2005a) 17:1685–1703.
Wang X, Li X, Meisenhelder J, Hunter T, Yoshida S, Asami T, Chory J. Autoregulation and homodimerization are involved in the activation of the plant steroid receptor BRI1. Developmental Cell (2005b) 8:855–865.[CrossRef][Web of Science][Medline]
Xu WH, Wang YS, Liu GZ, Chen X, Tinjuangjun P, Pi LY, Song WY. The autophosphorylated Ser686, Thr688, and Ser689 residues in the intracellular juxtamembrane domain of XA21 are implicated in stability control of rice receptor-like kinase. The Plant Journal (2006) 45:740–751.[CrossRef][Web of Science][Medline]
Zervas CG, Brown NH. Integrin adhesion: when is a kinase a kinase? Current Biology (2002) 12:R350–R351.[CrossRef][Web of Science][Medline]
Zervas CG, Gregory SL, Brown NH. Drosophila integrin-linked kinase is required at sites of integrin adhesion to link the cytoskeleton to the plasma membrane. Journal of Cell Biology (2001) 152:1007–1018.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. E. Leslie, M. W. Lewis, J.-Y. Youn, M. J. Daniels, and S. J. Liljegren The EVERSHED receptor-like kinase modulates floral organ shedding in Arabidopsis Development, February 1, 2010; 137(3): 467 - 476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-G. Kim, X. Li, J. A. Roden, K. W. Taylor, C. D. Aakre, B. Su, S. Lalonde, A. Kirik, Y. Chen, G. Baranage, et al. Xanthomonas T3S Effector XopN Suppresses PAMP-Triggered Immunity and Interacts with a Tomato Atypical Receptor-Like Kinase and TFT1 PLANT CELL, April 1, 2009; 21(4): 1305 - 1323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bayer, T. Nawy, C. Giglione, M. Galli, T. Meinnel, and W. Lukowitz Paternal Control of Embryonic Patterning in Arabidopsis thaliana Science, March 13, 2009; 323(5920): 1485 - 1488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-L. Xu, A. Rahman, T. I. Baskin, and J. J. Kieber Two Leucine-Rich Repeat Receptor Kinases Mediate Signaling, Linking Cell Wall Biosynthesis and ACC Synthase in Arabidopsis PLANT CELL, November 1, 2008; 20(11): 3065 - 3079. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||