1zsg Citations

Structural analysis of the SH3 domain of beta-PIX and its interaction with alpha-p21 activated kinase (PAK).

Biochemistry 44 10977-83 (2005)
Cited: 27 times
EuropePMC logo PMID: 16101281

Abstract

The PAK Ser/Thr kinases are important downstream effectors of the Rho family GTPases Cdc42 and Rac, partly mediating the role of these G proteins in cell proliferation and cytoskeletal rearrangements. As well as small G proteins, PAK interacts with the Cdc42/Rac exchange factor beta-PIX via the PIX SH3 domain and a nontypical Pro-rich region in PAK. This interaction is thought to affect the localization of PAK, as well as increased GTP/GDP exchange of Rac and Cdc42. We have determined the structure of the PIX-SH3/PAK peptide complex and shown that it differs from typical Src-like SH3/peptide complexes. The peptide makes contacts through the Pro-rich sequence in a similar way to standard SH3/peptide complexes, even though the Pro residue positions are not conserved. In addition, there are interactions with a Pro and Lys in the PAK, which are C-terminal to the conserved Arg found in all SH3-binding sequences. These contact a fourth binding pocket on the SH3 domain. We have measured the affinity of PIX-SH3 for the PAK peptide and found that it is of intermediate affinity. When PAK is activated, Ser-199 in the PIX-binding site is phosphorylated. This phosphorylation is sufficient to reduce the affinity for PIX 6-fold.

Articles - 1zsg mentioned but not cited (2)

  1. A proposed syntax for Minimotif Semantics, version 1. Vyas J, Nowling RJ, Maciejewski MW, Rajasekaran S, Gryk MR, Schiller MR. BMC Genomics 10 360 (2009)
  2. The Binding of Syndapin SH3 Domain to Dynamin Proline-rich Domain Involves Short and Long Distance Elements. Luo L, Xue J, Kwan A, Gamsjaeger R, Wielens J, von Kleist L, Cubeddu L, Guo Z, Stow JL, Parker MW, Mackay JP, Robinson PJ. J. Biol. Chem. 291 9411-9424 (2016)


Reviews citing this publication (8)

  1. Calmodulin-kinases: modulators of neuronal development and plasticity. Wayman GA, Lee YS, Tokumitsu H, Silva AJ, Soderling TR. Neuron 59 914-931 (2008)
  2. SH3 domain ligand binding: What's the consensus and where's the specificity? Saksela K, Permi P. FEBS Lett. 586 2609-2614 (2012)
  3. Deconstructing signal transduction pathways that regulate the actin cytoskeleton in dendritic spines. Penzes P, Cahill ME. Cytoskeleton (Hoboken) 69 426-441 (2012)
  4. p53 regulation of podosome formation and cellular invasion in vascular smooth muscle cells. Mak AS. Cell Adh Migr 5 144-149 (2011)
  5. Deconstructing signal transduction pathways that regulate the actin cytoskeleton in dendritic spines. Penzes P, Cahill ME. Cytoskeleton (Hoboken) 69 426-441 (2012)
  6. SH3 domain ligand binding: What's the consensus and where's the specificity? Saksela K, Permi P. FEBS Lett. 586 2609-2614 (2012)
  7. p53 regulation of podosome formation and cellular invasion in vascular smooth muscle cells. Mak AS. Cell Adh Migr 5 144-149 (2011)
  8. Calmodulin-kinases: modulators of neuronal development and plasticity. Wayman GA, Lee YS, Tokumitsu H, Silva AJ, Soderling TR. Neuron 59 914-931 (2008)

Articles citing this publication (17)

  1. Targeting and activation of Rac1 are mediated by the exchange factor beta-Pix. ten Klooster JP, Jaffer ZM, Chernoff J, Hordijk PL. J. Cell Biol. 172 759-769 (2006)
  2. Activity-dependent synaptogenesis: regulation by a CaM-kinase kinase/CaM-kinase I/betaPIX signaling complex. Saneyoshi T, Wayman G, Fortin D, Davare M, Hoshi N, Nozaki N, Natsume T, Soderling TR. Neuron 57 94-107 (2008)
  3. Scrib controls Cdc42 localization and activity to promote cell polarization during astrocyte migration. Osmani N, Vitale N, Borg JP, Etienne-Manneville S. Curr. Biol. 16 2395-2405 (2006)
  4. Cdc42 localization and cell polarity depend on membrane traffic. Osmani N, Peglion F, Chavrier P, Etienne-Manneville S. J. Cell Biol. 191 1261-1269 (2010)
  5. Induction of vascular permeability: beta PIX and GIT1 scaffold the activation of extracellular signal-regulated kinase by PAK. Stockton R, Reutershan J, Scott D, Sanders J, Ley K, Schwartz MA. Mol. Biol. Cell 18 2346-2355 (2007)
  6. Role of phospholipase Cgamma1 in cell spreading requires association with a beta-Pix/GIT1-containing complex, leading to activation of Cdc42 and Rac1. Jones NP, Katan M. Mol. Cell. Biol. 27 5790-5805 (2007)
  7. The X-linked lymphoproliferative disease gene product SAP associates with PAK-interacting exchange factor and participates in T cell activation. Gu C, Tangye SG, Sun X, Luo Y, Lin Z, Wu J. Proc. Natl. Acad. Sci. U.S.A. 103 14447-14452 (2006)
  8. Synaptic plasticity, a symphony in GEF. Kiraly DD, Eipper-Mains JE, Mains RE, Eipper BA. ACS Chem Neurosci 1 348-365 (2010)
  9. Crystal structure of the SH3 domain of betaPIX in complex with a high affinity peptide from PAK2. Hoelz A, Janz JM, Lawrie SD, Corwin B, Lee A, Sakmar TP. J. Mol. Biol. 358 509-522 (2006)
  10. PAK1 and PAK2 have different roles in HGF-induced morphological responses. Bright MD, Garner AP, Ridley AJ. Cell. Signal. 21 1738-1747 (2009)
  11. Quantitative relation between intermolecular and intramolecular binding of pro-rich peptides to SH3 domains. Zhou HX. Biophys. J. 91 3170-3181 (2006)
  12. Structural, functional, and bioinformatic studies demonstrate the crucial role of an extended peptide binding site for the SH3 domain of yeast Abp1p. Stollar EJ, Garcia B, Chong PA, Rath A, Lin H, Forman-Kay JD, Davidson AR. J. Biol. Chem. 284 26918-26927 (2009)
  13. LAT-independent Erk activation via Bam32-PLC-γ1-Pak1 complexes: GTPase-independent Pak1 activation. Rouquette-Jazdanian AK, Sommers CL, Kortum RL, Morrison DK, Samelson LE. Mol. Cell 48 298-312 (2012)
  14. Identification of phosphorylation sites in betaPIX and PAK1. Mayhew MW, Jeffery ED, Sherman NE, Nelson K, Polefrone JM, Pratt SJ, Shabanowitz J, Parsons JT, Fox JW, Hunt DF, Horwitz AF. J. Cell. Sci. 120 3911-3918 (2007)
  15. Cas utilizes Nck2 to activate Cdc42 and regulate cell polarization during cell migration in response to wound healing. Funasaka K, Ito S, Hasegawa H, Goldberg GS, Hirooka Y, Goto H, Hamaguchi M, Senga T. FEBS J. 277 3502-3513 (2010)
  16. 3D structure analysis of PAKs: A clue to the rational design for affinity reagents and blockers. Jha RK, Strauss CE. Cell Logist 2 69-77 (2012)
  17. Crystal structure of the N-terminal SH3 domain of mouse betaPIX, p21-activated kinase-interacting exchange factor. Li X, Liu X, Sun F, Gao J, Zhou H, Gao GF, Bartlam M, Rao Z. Biochem. Biophys. Res. Commun. 339 407-414 (2006)