| Structural highlights
Function
[BEM1_YEAST] Necessary for cell polarization during vegetative growth. May link the cytoskeleton to morphogenic determinants on the cell surface.[1] [STE20_YEAST] MAP4K component of the MAPK pathway required for the mating pheromone response, haploid invasive growth and diploid pseudohyphal development. Links the pheromone response G-protein beta gamma subunits to downstream signaling components. Needed for mating in haploid cells, induction of a mating-specific gene FUS1, induction of mating-specific morphologies, and pheromone-induced proliferation arrest. Required for the regulation of the actin polarization and bud emergence during cell cycle in G1. Involved in the high osmolarity glycerol (HOG) response. Phosphorylates 'Thr-307' and 'Ser-302' or 'Ser-306' of STE11 and 'Ser-357' of MYO3. Phosphorylates histone H2B to form H2BS10ph during meiosis and H(2)O(2)-induced apoptosis. Its interaction with CDC42 is required for both invasive growth and the formation of pseudohyphae. Its interaction with STE4 is required for the pheromone signaling.[2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Bem1 is a scaffold protein essential for the establishment of cell polarity in Saccharomyces cerevisiae. This work reports the solution structure of a Cdc42 binding module of Bem1 comprising the second SH3 domain (SH3b) and its C-terminal flanking region termed Cdc42 interacting (CI). First, the structure of Bem1 SH3b-CI was determined by NMR spectroscopy, which shows that Bem1 SH3b-CI is a structurally and functionally related domain that binds Cdc42. Next, the solution structure of Bem1 SH3b-CI in complex with the proline-rich region of p21-activated kinase Ste20 (Ste20 PRR) was determined. Finally, the interaction surface of Bem1 SH3b-CI with Cdc42 was identified based on chemical shift perturbation studies which reveals that Bem1 SH3b-CI interacts simultaneously with both Ste20 PRR and Cdc42 using the opposite surfaces. Thus, Bem1 can tether Cdc42 and Ste20 in close proximity so that Cdc42 can efficiently interact with Ste20 Cdc42 and Rac interactive binding (CRIB). Based on the present results together with the previous biochemical studies (Lamson, R. E., Winters, M. J., and Pryciak, P. M. (2002) Mol. Cell. Biol. 22, 2939-2951 and Winters, M. J., and Pryciak, P. M. (2005) Mol. Cell. Biol. 25, 2177-2190), a model was suggested that the autoinhibition of Ste20 kinase activity by CRIB is released through the Cdc42-CRIB interaction, which is mediated by Bem1, and Ste20 is subsequently activated, an initial step for the establishment of the cell polarity.
Solution structure of a novel Cdc42 binding module of Bem1 and its interaction with Ste20 and Cdc42.,Takaku T, Ogura K, Kumeta H, Yoshida N, Inagaki F J Biol Chem. 2010 Jun 18;285(25):19346-53. Epub 2010 Apr 21. PMID:20410294[22]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gao XD, Sperber LM, Kane SA, Tong Z, Tong AH, Boone C, Bi E. Sequential and distinct roles of the cadherin domain-containing protein Axl2p in cell polarization in yeast cell cycle. Mol Biol Cell. 2007 Jul;18(7):2542-60. Epub 2007 Apr 25. PMID:17460121 doi:http://dx.doi.org/10.1091/mbc.E06-09-0822
- ↑ Leberer E, Dignard D, Harcus D, Thomas DY, Whiteway M. The protein kinase homologue Ste20p is required to link the yeast pheromone response G-protein beta gamma subunits to downstream signalling components. EMBO J. 1992 Dec;11(13):4815-24. PMID:1464311
- ↑ Ramer SW, Davis RW. A dominant truncation allele identifies a gene, STE20, that encodes a putative protein kinase necessary for mating in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):452-6. PMID:8421676
- ↑ Wu C, Whiteway M, Thomas DY, Leberer E. Molecular characterization of Ste20p, a potential mitogen-activated protein or extracellular signal-regulated kinase kinase (MEK) kinase kinase from Saccharomyces cerevisiae. J Biol Chem. 1995 Jul 7;270(27):15984-92. PMID:7608157
- ↑ Peter M, Neiman AM, Park HO, van Lohuizen M, Herskowitz I. Functional analysis of the interaction between the small GTP binding protein Cdc42 and the Ste20 protein kinase in yeast. EMBO J. 1996 Dec 16;15(24):7046-59. PMID:9003780
- ↑ Akada R, Kallal L, Johnson DI, Kurjan J. Genetic relationships between the G protein beta gamma complex, Ste5p, Ste20p and Cdc42p: investigation of effector roles in the yeast pheromone response pathway. Genetics. 1996 May;143(1):103-17. PMID:8722766
- ↑ Mosch HU, Roberts RL, Fink GR. Ras2 signals via the Cdc42/Ste20/mitogen-activated protein kinase module to induce filamentous growth in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5352-6. PMID:8643578
- ↑ Leberer E, Wu C, Leeuw T, Fourest-Lieuvin A, Segall JE, Thomas DY. Functional characterization of the Cdc42p binding domain of yeast Ste20p protein kinase. EMBO J. 1997 Jan 2;16(1):83-97. PMID:9009270 doi:http://dx.doi.org/10.1093/emboj/16.1.83
- ↑ Wu C, Lytvyn V, Thomas DY, Leberer E. The phosphorylation site for Ste20p-like protein kinases is essential for the function of myosin-I in yeast. J Biol Chem. 1997 Dec 5;272(49):30623-6. PMID:9388196
- ↑ Eby JJ, Holly SP, van Drogen F, Grishin AV, Peter M, Drubin DG, Blumer KJ. Actin cytoskeleton organization regulated by the PAK family of protein kinases. Curr Biol. 1998 Aug 27;8(17):967-70. PMID:9742399
- ↑ Leeuw T, Wu C, Schrag JD, Whiteway M, Thomas DY, Leberer E. Interaction of a G-protein beta-subunit with a conserved sequence in Ste20/PAK family protein kinases. Nature. 1998 Jan 8;391(6663):191-5. PMID:9428767 doi:http://dx.doi.org/10.1038/34448
- ↑ Holly SP, Blumer KJ. PAK-family kinases regulate cell and actin polarization throughout the cell cycle of Saccharomyces cerevisiae. J Cell Biol. 1999 Nov 15;147(4):845-56. PMID:10562285
- ↑ Drogen F, O'Rourke SM, Stucke VM, Jaquenoud M, Neiman AM, Peter M. Phosphorylation of the MEKK Ste11p by the PAK-like kinase Ste20p is required for MAP kinase signaling in vivo. Curr Biol. 2000 Jun 1;10(11):630-9. PMID:10837245
- ↑ Raitt DC, Posas F, Saito H. Yeast Cdc42 GTPase and Ste20 PAK-like kinase regulate Sho1-dependent activation of the Hog1 MAPK pathway. EMBO J. 2000 Sep 1;19(17):4623-31. PMID:10970855 doi:http://dx.doi.org/10.1093/emboj/19.17.4623
- ↑ Moskow JJ, Gladfelter AS, Lamson RE, Pryciak PM, Lew DJ. Role of Cdc42p in pheromone-stimulated signal transduction in Saccharomyces cerevisiae. Mol Cell Biol. 2000 Oct;20(20):7559-71. PMID:11003652
- ↑ Lamson RE, Winters MJ, Pryciak PM. Cdc42 regulation of kinase activity and signaling by the yeast p21-activated kinase Ste20. Mol Cell Biol. 2002 May;22(9):2939-51. PMID:11940652
- ↑ Goehring AS, Mitchell DA, Tong AH, Keniry ME, Boone C, Sprague GF Jr. Synthetic lethal analysis implicates Ste20p, a p21-activated potein kinase, in polarisome activation. Mol Biol Cell. 2003 Apr;14(4):1501-16. PMID:12686605 doi:http://dx.doi.org/10.1091/mbc.E02-06-0348
- ↑ Keniry ME, Sprague GF Jr. Identification of p21-activated kinase specificity determinants in budding yeast: a single amino acid substitution imparts Ste20 specificity to Cla4. Mol Cell Biol. 2003 Mar;23(5):1569-80. PMID:12588977
- ↑ Ahn SH, Cheung WL, Hsu JY, Diaz RL, Smith MM, Allis CD. Sterile 20 kinase phosphorylates histone H2B at serine 10 during hydrogen peroxide-induced apoptosis in S. cerevisiae. Cell. 2005 Jan 14;120(1):25-36. PMID:15652479 doi:S009286740401092X
- ↑ Ahn SH, Henderson KA, Keeney S, Allis CD. H2B (Ser10) phosphorylation is induced during apoptosis and meiosis in S. cerevisiae. Cell Cycle. 2005 Jun;4(6):780-3. Epub 2005 Jun 14. PMID:15970663
- ↑ Winters MJ, Pryciak PM. Interaction with the SH3 domain protein Bem1 regulates signaling by the Saccharomyces cerevisiae p21-activated kinase Ste20. Mol Cell Biol. 2005 Mar;25(6):2177-90. PMID:15743816 doi:http://dx.doi.org/25/6/2177
- ↑ Takaku T, Ogura K, Kumeta H, Yoshida N, Inagaki F. Solution structure of a novel Cdc42 binding module of Bem1 and its interaction with Ste20 and Cdc42. J Biol Chem. 2010 Jun 18;285(25):19346-53. Epub 2010 Apr 21. PMID:20410294 doi:10.1074/jbc.M110.116749
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