| Structural highlights
Function
[NBP2_YEAST] Negatively regulates the high-osmolarity glycerol (HOG) pathway through its negative regulation of the HOG1 kinase activity. Mediates the binding between the PTC1 phosphatase and the PBS2 MAP/ERK kinase (MEK). With PTC1, regulates endoplasmic reticulum inheritance through the cell wall integrity (CWI) MAPK pathway by modulating the MAPK, SLT2.[1] [2] [3] [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.[4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23]
Publication Abstract from PubMed
The yeast Nbp2p SH3 and Bem1p SH3b domains bind certain target peptides with similar high affinities, yet display vastly different affinities for other targets. To investigate this unusual behavior, we have solved the structure of the Nbp2p SH3-Ste20 peptide complex and compared it with the previously determined structure of the Bem1p SH3b bound to the same peptide. Although the Ste20 peptide interacts with both domains in a structurally similar manner, extensive in vitro studies with domain and peptide mutants revealed large variations in interaction strength across the binding interface of the two complexes. Whereas the Nbp2p SH3 made stronger contacts with the peptide core RXXPXXP motif, the Bem1p SH3b domain made stronger contacts with residues flanking the core motif. Remarkably, this modulation of local binding energetics can explain the distinct and highly nuanced binding specificities of these two domains.
Distinct Peptide Binding Specificities of Src Homology 3 (SH3) Protein Domains Can Be Determined by Modulation of Local Energetics across the Binding Interface.,Gorelik M, Davidson AR J Biol Chem. 2012 Mar 16;287(12):9168-77. Epub 2012 Jan 25. PMID:22277653[24]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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- ↑ Mapes J, Ota IM. Nbp2 targets the Ptc1-type 2C Ser/Thr phosphatase to the HOG MAPK pathway. EMBO J. 2004 Jan 28;23(2):302-11. Epub 2003 Dec 18. PMID:14685261 doi:http://dx.doi.org/10.1038/sj.emboj.7600036
- ↑ Du Y, Walker L, Novick P, Ferro-Novick S. Ptc1p regulates cortical ER inheritance via Slt2p. EMBO J. 2006 Oct 4;25(19):4413-22. Epub 2006 Sep 14. PMID:16977319 doi:http://dx.doi.org/10.1038/sj.emboj.7601319
- ↑ 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
- ↑ Gorelik M, Davidson AR. 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 Mar 16;287(12):9168-77. Epub 2012 Jan 25. PMID:22277653 doi:10.1074/jbc.M111.330753
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