Genomes and Genes
Gene Symbol: CLA4
Description: serine/threonine protein kinase CLA4
Alias: ERC10, serine/threonine protein kinase CLA4
Species: Saccharomyces cerevisiae S288c
- Gladfelter A, Moskow J, Zyla T, Lew D. Isolation and characterization of effector-loop mutants of CDC42 in yeast. Mol Biol Cell. 2001;12:1239-55 pubmed..The availability of partial function alleles of CDC42 in a genetically tractable system serves as a useful starting point for genetic approaches to identify such novel effectors. ..
- Gulli M, Jaquenoud M, Shimada Y, Niederhauser G, Wiget P, Peter M. Phosphorylation of the Cdc42 exchange factor Cdc24 by the PAK-like kinase Cla4 may regulate polarized growth in yeast. Mol Cell. 2000;6:1155-67 pubmed..activated Cdc42 then polarizes the cytoskeleton in a manner dependent on its effectors Bni1 and the PAK-like kinase Cla4. In addition, Cla4 induces phosphorylation of Cdc24, leading to its dissociation from Bem1 at bud tips, thereby ..
- Wu C, Lytvyn V, Thomas D, Leberer E. The phosphorylation site for Ste20p-like protein kinases is essential for the function of myosin-I in yeast. J Biol Chem. 1997;272:30623-6 pubmed..Our results suggest that phosphorylation of the head domain by Ste20p-like protein kinases plays an essential role in the function of myosin-I in yeast cells. ..
- Weiss E, Bishop A, Shokat K, Drubin D. Chemical genetic analysis of the budding-yeast p21-activated kinase Cla4p. Nat Cell Biol. 2000;2:677-85 pubmed..Here we define the in vivo function of the kinase activity of the budding yeast PAK Cla4p, using cla4 alleles that are specifically inhibited by a cell-permeable compound that does not inhibit the wild-type kinase...
- Artiles K, Anastasia S, McCusker D, Kellogg D. The Rts1 regulatory subunit of protein phosphatase 2A is required for control of G1 cyclin transcription and nutrient modulation of cell size. PLoS Genet. 2009;5:e1000727 pubmed publisher..Together, these observations demonstrate that Rts1 is a key player in pathways that link nutrient availability, cell size, and G1 cyclin transcription. Since Rts1 is highly conserved, it may function in similar pathways in vertebrates. ..
- Chiroli E, Fraschini R, Beretta A, Tonelli M, Lucchini G, Piatti S. Budding yeast PAK kinases regulate mitotic exit by two different mechanisms. J Cell Biol. 2003;160:857-74 pubmedWe report the characterization of the dominant-negative CLA4t allele of the budding yeast CLA4 gene, encoding a member of the p21-activated kinase (PAK) family of protein kinases, which, together with its homologue STE20, plays an ..
- Fraschini R, D Ambrosio C, Venturetti M, Lucchini G, Piatti S. Disappearance of the budding yeast Bub2-Bfa1 complex from the mother-bound spindle pole contributes to mitotic exit. J Cell Biol. 2006;172:335-46 pubmed..Moreover, it correlates with the passage of one spindle pole through the bud neck because it needs septin ring formation and bud neck kinases. ..
- Sreenivasan A, Kellogg D. The elm1 kinase functions in a mitotic signaling network in budding yeast. Mol Cell Biol. 1999;19:7983-94 pubmed..the function of a Clb2-binding protein called Nap1, the Cdc42 GTPase, and two protein kinases called Gin4 and Cla4. In this study, we demonstrate that the Elm1 kinase also plays a role in the control of bud growth during mitosis...
- Raitt D, Posas F, Saito H. Yeast Cdc42 GTPase and Ste20 PAK-like kinase regulate Sho1-dependent activation of the Hog1 MAPK pathway. EMBO J. 2000;19:4623-31 pubmed..Since activated Cdc42 translocates Ste20 to sites of polarized growth, the upstream and downstream elements of the HOG pathway are brought together through the membrane targeting function of Sho1 and Cdc42. ..
- Asano S, Park J, Sakchaisri K, Yu L, Song S, Supavilai P, et al. Concerted mechanism of Swe1/Wee1 regulation by multiple kinases in budding yeast. EMBO J. 2005;24:2194-204 pubmed..We propose that the concerted action of Cdc28/Cdk1 and Cdc5/Polo on their common substrates is an evolutionarily conserved mechanism that is crucial for effectively triggering mitotic entry and other critical mitotic events. ..
- Sakchaisri K, Asano S, Yu L, Shulewitz M, Park C, Park J, et al. Coupling morphogenesis to mitotic entry. Proc Natl Acad Sci U S A. 2004;101:4124-9 pubmed..Here, we show that two other kinases targeted sequentially to the neck, Cla4/PAK and Cdc5/Polo, are responsible for stepwise phosphorylation and down-regulation of Swe1...
- Chen G, Kim Y, Chan C. The Cdc42 GTPase-associated proteins Gic1 and Gic2 are required for polarized cell growth in Saccharomyces cerevisiae. Genes Dev. 1997;11:2958-71 pubmed..The ability of Gic1 to associate with Cdc42 is important for its function but is apparently not essential for its subcellular localization. ..
- Fraschini R, Bilotta D, Lucchini G, Piatti S. Functional characterization of Dma1 and Dma2, the budding yeast homologues of Schizosaccharomyces pombe Dma1 and human Chfr. Mol Biol Cell. 2004;15:3796-810 pubmed..Although their primary functions remain to be defined, our data suggest that Dma1 and Dma2 might be required to ensure timely MEN activation in telophase. ..
- Versele M, Thorner J. Septin collar formation in budding yeast requires GTP binding and direct phosphorylation by the PAK, Cla4. J Cell Biol. 2004;164:701-15 pubmed..Absence of a p21-activated protein kinase (Cla4) perturbs septin collar formation...
- Bertazzi D, Kurtulmus B, Pereira G. The cortical protein Lte1 promotes mitotic exit by inhibiting the spindle position checkpoint kinase Kin4. J Cell Biol. 2011;193:1033-48 pubmed publisher..This Lte1-mediated exclusion of Kin4 from the dSPB is essential for proper mitotic exit of cells with a correctly aligned spindle. Therefore, Lte1 promotes mitotic exit by inhibiting Kin4 activity at the dSPB. ..
- Holly S, Blumer K. PAK-family kinases regulate cell and actin polarization throughout the cell cycle of Saccharomyces cerevisiae. J Cell Biol. 1999;147:845-56 pubmed..Inactivation of the PAK homologues Ste20 and Cla4 at various points in the cell cycle resulted in loss of cell and actin cytoskeletal polarity, but not in ..
- Gladfelter A, Zyla T, Lew D. Genetic interactions among regulators of septin organization. Eukaryot Cell. 2004;3:847-54 pubmed..strains containing single or multiple mutations in eight septin organization genes (CDC42, RGA1, RGA2, BEM3, CLA4, GIN4, NAP1, and ELM1)...
- Kozubowski L, Saito K, Johnson J, Howell A, Zyla T, Lew D. Symmetry-breaking polarization driven by a Cdc42p GEF-PAK complex. Curr Biol. 2008;18:1719-26 pubmed publisher..Our findings provide mechanistic insight into an evolutionarily conserved pattern-forming positive-feedback pathway. ..
- Höfken T, Schiebel E. A role for cell polarity proteins in mitotic exit. EMBO J. 2002;21:4851-62 pubmed..The Rho-like GTPase Cdc42, its GEF Cdc24 and its effector Cla4 [a member of the p21-activated kinases (PAKs)] control the initial binding and activation of Lte1 to the bud cortex...
- Bose I, Irazoqui J, Moskow J, Bardes E, Zyla T, Lew D. Assembly of scaffold-mediated complexes containing Cdc42p, the exchange factor Cdc24p, and the effector Cla4p required for cell cycle-regulated phosphorylation of Cdc24p. J Biol Chem. 2001;276:7176-86 pubmed..We suggest that Bem1p acts to concentrate polarity establishment proteins at a discrete site, facilitating polarization and promoting Cdc24p phosphorylation at specific times during the cell cycle. ..
- Merlini L, Bolognesi A, Juanes M, Vandermoere F, Courtellemont T, Pascolutti R, et al. Rho1- and Pkc1-dependent phosphorylation of the F-BAR protein Syp1 contributes to septin ring assembly. Mol Biol Cell. 2015;26:3245-62 pubmed publisher..We propose that Rho1 and Pkc1 coordinate septin ring assembly with membrane and cell wall remodeling partly by controlling Syp1 residence at the bud neck. ..
- Mösch H, Kohler T, Braus G. Different domains of the essential GTPase Cdc42p required for growth and development of Saccharomyces cerevisiae. Mol Cell Biol. 2001;21:235-48 pubmed
- Howe A, Fairn G, Macdonald K, Bankaitis V, McMaster C. Regulation of phosphoinositide levels by the phospholipid transfer protein Sec14p controls Cdc42p/p21-activated kinase-mediated cell cycle progression at cytokinesis. Eukaryot Cell. 2007;6:1814-23 pubmed..of phosphatidylinositol 4-kinases and phosphatidylinositol 4-phosphate 5-kinase prevented growth arrest by CDC42, CLA4, or STE20 upon inactivation of Sec14p function...
- Seshan A, Amon A. Ras and the Rho effector Cla4 collaborate to target and anchor Lte1 at the bud cortex. Cell Cycle. 2005;4:940-6 pubmed..Ras, the Rho GTPase Cdc42 and its effector the protein kinase Cla4 are required for Lte1's association with the bud cortex...
- Richman T, Johnson D. Saccharomyces cerevisiae cdc42p GTPase is involved in preventing the recurrence of bud emergence during the cell cycle. Mol Cell Biol. 2000;20:8548-59 pubmed
- Bi E, Chiavetta J, Chen H, Chen G, Chan C, Pringle J. Identification of novel, evolutionarily conserved Cdc42p-interacting proteins and of redundant pathways linking Cdc24p and Cdc42p to actin polarization in yeast. Mol Biol Cell. 2000;11:773-93 pubmed..designed to identify possible additional targets of Cdc24p instead identified two previously known genes, MSB1 and CLA4, and one novel gene, designated MSB3, all of which appear to function in the Cdc24p-Cdc42p pathway...
- Merlini L, Fraschini R, Boettcher B, Barral Y, Lucchini G, Piatti S. Budding yeast dma proteins control septin dynamics and the spindle position checkpoint by promoting the recruitment of the Elm1 kinase to the bud neck. PLoS Genet. 2012;8:e1002670 pubmed publisher..Altogether, our data indicate that septin dynamics and SPOC function are intimately linked and support the idea that integrity of the bud neck is crucial for SPOC signalling. ..
- Bartholomew C, Hardy C. p21-activated kinases Cla4 and Ste20 regulate vacuole inheritance in Saccharomyces cerevisiae. Eukaryot Cell. 2009;8:560-72 pubmed publisher..The p21-activated kinases (PAKs) Cla4 and Ste20 are localized to and activated in the bud...
- Mayer M, Pot I, Chang M, Xu H, Aneliunas V, Kwok T, et al. Identification of protein complexes required for efficient sister chromatid cohesion. Mol Biol Cell. 2004;15:1736-45 pubmed..Furthermore, we find that genes involved in mitotic spindle integrity and positioning have a previously unrecognized role in sister chromatid cohesion. ..
- Souid A, Gao C, Wang L, Milgrom E, Shen W. ELM1 is required for multidrug resistance in Saccharomyces cerevisiae. Genetics. 2006;173:1919-37 pubmed..Collectively, these data show that ELM1, and genes encoding related serine/threonine protein kinases, are required for regulation of multidrug resistance involving, at least in part, control of PDR5 transcription...
- Tatebayashi K, Yamamoto K, Tanaka K, Tomida T, Maruoka T, Kasukawa E, et al. Adaptor functions of Cdc42, Ste50, and Sho1 in the yeast osmoregulatory HOG MAPK pathway. EMBO J. 2006;25:3033-44 pubmed..We found that Cdc42, in addition to binding and activating the PAK-like kinases Ste20 and Cla4, binds to the Ste11-Ste50 complex to bring activated Ste20/Cla4 to their substrate Ste11...
- McMurray M, Stefan C, Wemmer M, Odorizzi G, Emr S, Thorner J. Genetic interactions with mutations affecting septin assembly reveal ESCRT functions in budding yeast cytokinesis. Biol Chem. 2011;392:699-712 pubmed publisher..We show here that mutations in ESCRT-encoding genes exacerbate the cytokinesis defects of cla4? or elm1? mutants, in which septin assembly is perturbed at an early stage in cell division, and alleviate ..
- Oehlen L, Cross F. Potential regulation of Ste20 function by the Cln1-Cdc28 and Cln2-Cdc28 cyclin-dependent protein kinases. J Biol Chem. 1998;273:25089-97 pubmed
- Takahashi S, Pryciak P. Identification of novel membrane-binding domains in multiple yeast Cdc42 effectors. Mol Biol Cell. 2007;18:4945-56 pubmed
- Goehring A, Rivers D, Sprague G. Urmylation: a ubiquitin-like pathway that functions during invasive growth and budding in yeast. Mol Biol Cell. 2003;14:4329-41 pubmed..Moreover, these five genes have a role in invasive growth and display genetic interactions with the TOR pathway. In summary, our results suggest the urmylation pathway is involved in nutrient sensing and budding. ..
- Richman T, Toenjes K, Morales S, Cole K, Wasserman B, Taylor C, et al. Analysis of cell-cycle specific localization of the Rdi1p RhoGDI and the structural determinants required for Cdc42p membrane localization and clustering at sites of polarized growth. Curr Genet. 2004;45:339-49 pubmed..Taken together, these results provide insight into the complicated nature of the relationships between Cdc42p localization, nucleotide binding, and protein-protein interactions. ..
- Meitinger F, Khmelinskii A, Morlot S, Kurtulmus B, Palani S, Andrés Pons A, et al. A memory system of negative polarity cues prevents replicative aging. Cell. 2014;159:1056-1069 pubmed publisher..Our work thus established CRMs as negative polarity cues that prevent Cdc42 reactivation to sustain the fitness of replicating cells. ..
- Legesse Miller A, Zhang S, Santiago Tirado F, Van Pelt C, Bretscher A. Regulated phosphorylation of budding yeast's essential myosin V heavy chain, Myo2p. Mol Biol Cell. 2006;17:1812-21 pubmed..These results suggest that in yeast, Myo2p is subject to phosphoregulation involving a PKA-related signaling pathway. ..
- Enserink J, Smolka M, Zhou H, Kolodner R. Checkpoint proteins control morphogenetic events during DNA replication stress in Saccharomyces cerevisiae. J Cell Biol. 2006;175:729-41 pubmed..Thus, checkpoint proteins play an important role in coordinating morphogenetic events with DNA replication during replication stress. ..
- Hsieh Y, Hung P, Leu J. Hsp90 regulates nongenetic variation in response to environmental stress. Mol Cell. 2013;50:82-92 pubmed publisher..The morphological heterogeneity is driven by the dosage of Cdc28 and Cla4, a key regulator of septin formation...
- Smith G, Givan S, Cullen P, Sprague G. GTPase-activating proteins for Cdc42. Eukaryot Cell. 2002;1:469-80 pubmed..Thus, it appears that the GAPs play a role in modulating specific aspects of Cdc42 function. Alternatively, the different phenotypes could reflect quantitative rather than qualitative differences in GAP activity in the mutant strains. ..
- Kim J, Rose M. Stable Pseudohyphal Growth in Budding Yeast Induced by Synergism between Septin Defects and Altered MAP-kinase Signaling. PLoS Genet. 2015;11:e1005684 pubmed publisher..Taken together, our findings show that budding yeast can access a stable constitutive pseudohyphal growth state with very few genetic and regulatory changes. ..
- Meitinger F, Richter H, Heisel S, Hub B, Seufert W, Pereira G. A safeguard mechanism regulates Rho GTPases to coordinate cytokinesis with the establishment of cell polarity. PLoS Biol. 2013;11:e1001495 pubmed publisher..Our findings provide unexpected insights into the temporal control of cytokinesis and describe the importance of a Gps1-dependent mechanism for highly accurate polarity switching between two closely connected locations. ..
- Yau R, Wong S, Weisman L. Spatial regulation of organelle release from myosin V transport by p21-activated kinases. J Cell Biol. 2017;216:1557-1566 pubmed publisher..We demonstrate that upon arrival at the bud cortex, Vac17 is phosphorylated by Cla4. Cla4-dependent phosphorylation is required for the ubiquitylation and subsequent degradation of Vac17 and the ..
- Lin M, Grillitsch K, Daum G, Just U, Höfken T. Modulation of sterol homeostasis by the Cdc42p effectors Cla4p and Ste20p in the yeast Saccharomyces cerevisiae. FEBS J. 2009;276:7253-64 pubmed..b>CLA4 interacts genetically with ERG4 and NCP1...
- Traven A, Beilharz T, Lo T, Lueder F, Preiss T, Heierhorst J. The Ccr4-Pop2-NOT mRNA deadenylase contributes to septin organization in Saccharomyces cerevisiae. Genetics. 2009;182:955-66 pubmed publisher..mRNAs encoding regulators of septin assembly (Ccd42, Cdc24, Rga1, Rga2, Bem3, Gin4, Cla4, and Elm1) presented with short poly(A) tails at steady state in wild-type (wt) cells, suggesting their translation ..
- Iwase M, Toh e A. Ybr267w is a new cytoplasmic protein belonging to the mitotic signaling network of Saccharomyces cerevisiae. Cell Struct Funct. 2004;29:1-15 pubmed..In view of the fact that members belonging to the mitotic signaling network are localized to the bud neck, at least at some stage of the cell cycle, Rei1 is a unique component of this pathway. ..
- Blanco N, Reidy M, Arroyo J, Cabib E. Crosslinks in the cell wall of budding yeast control morphogenesis at the mother-bud neck. J Cell Sci. 2012;125:5781-9 pubmed publisherPrevious work has shown that, in cla4? cells of budding yeast, where septin ring organization is compromised, the chitin ring at the mother-daughter neck becomes essential for prevention of neck widening and for cytokinesis...
- Kim J, Rose M. A mechanism for the coordination of proliferation and differentiation by spatial regulation of Fus2p in budding yeast. Genes Dev. 2012;26:1110-21 pubmed publisher..Thus, potential premature activation of Fus2p in mitosis is prevented by cell cycle-dependent phosphorylation that overrides the mating pheromone-induced phosphorylation that drives nuclear export. ..
- Tiedje C, Holland D, Just U, Höfken T. Proteins involved in sterol synthesis interact with Ste20 and regulate cell polarity. J Cell Sci. 2007;120:3613-24 pubmed..Lack of CBR1 produced no detectable phenotype, whereas the deletion of CBR1 in the absence of NCP1 was lethal. Using a conditional lethal mutant we demonstrate that both proteins have overlapping functions in bud morphology. ..
- Heinrich M, Köhler T, Mösch H. Role of Cdc42-Cla4 interaction in the pheromone response of Saccharomyces cerevisiae. Eukaryot Cell. 2007;6:317-27 pubmed..Furthermore, Cdc42(V36A) and Cdc42(V36A, I182T) proteins show reduced interaction with the PAK Cla4 but not with Ste20...
- Lin M, Unden H, Jacquier N, Schneiter R, Just U, Höfken T. The Cdc42 effectors Ste20, Cla4, and Skm1 down-regulate the expression of genes involved in sterol uptake by a mitogen-activated protein kinase-independent pathway. Mol Biol Cell. 2009;20:4826-37 pubmed publisher..GTPase Cdc42 regulates polarized growth through its effectors, including the p21-activated kinases (PAKs) Ste20, Cla4, and Skm1...
- Davis C, Richman T, Deliduka S, Blaisdell J, Collins C, Johnson D. Analysis of the mechanisms of action of the Saccharomyces cerevisiae dominant lethal cdc42G12V and dominant negative cdc42D118A mutations. J Biol Chem. 1998;273:849-58 pubmed
- Johnson C, Weems A, Brewer J, Thorner J, McMurray M. Cytosolic chaperones mediate quality control of higher-order septin assembly in budding yeast. Mol Biol Cell. 2015;26:1323-44 pubmed publisher..These findings provide new roles for chaperone-mediated kinetic partitioning of non-native proteins and may help explain the etiology of septin-linked human diseases. ..
- Gorelik M, Davidson A. Distinct peptide binding specificities of Src homology 3 (SH3) protein domains can be determined by modulation of local energetics across the binding interface. J Biol Chem. 2012;287:9168-77 pubmed publisher..Remarkably, this modulation of local binding energetics can explain the distinct and highly nuanced binding specificities of these two domains. ..
- Richman T, Sawyer M, Johnson D. The Cdc42p GTPase is involved in a G2/M morphogenetic checkpoint regulating the apical-isotropic switch and nuclear division in yeast. J Biol Chem. 1999;274:16861-70 pubmed
- Smith S, Rubinstein B, Mendes Pinto I, Slaughter B, Unruh J, Li R. Independence of symmetry breaking on Bem1-mediated autocatalytic activation of Cdc42. J Cell Biol. 2013;202:1091-106 pubmed publisher..The model predicts a nonmonotonic dependence of cell polarization on the concentration of Rdi1 relative to that of Cdc42. ..
- Loewen C, Young B, Tavassoli S, Levine T. Inheritance of cortical ER in yeast is required for normal septin organization. J Cell Biol. 2007;179:467-83 pubmed..This perturbation leads to a delay in the transition through G2, activating the Saccharomyces wee1 kinase (Swe1) and the morphogenesis checkpoint. Thus, we identify a mechanism involved in sensing the distribution of ER. ..
- Leeuw T, Wu C, Schrag J, Whiteway M, Thomas D, Leberer E. Interaction of a G-protein beta-subunit with a conserved sequence in Ste20/PAK family protein kinases. Nature. 1998;391:191-5 pubmed
- Logan M, Jones L, Eitzen G. Cdc42p and Rho1p are sequentially activated and mechanistically linked to vacuole membrane fusion. Biochem Biophys Res Commun. 2010;394:64-9 pubmed publisher..These results define unique activation mechanisms for Cdc42p and Rho1p, which may be linked to the vacuole membrane fusion mechanism. ..