Regulation of CDC42 GTPase by proline-rich tyrosine kinase 2 interacting with PSGAP, a novel pleckstrin homology and Src homology 3 domain containing rhoGAP protein

Xiu Rong Ren, Quansheng Du, Yang Zhong Huang, Shi Zhou Ao, Lin Mei, Wencheng Xiong

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

Proline-rich tyrosine kinase 2 (PYK2), a tyrosine kinase structurally related to focal adhesion kinase (FAK), is implicated in regulating cytoskeletal organization. However, mechanisms by which PYK2 participates in and regulates cytoskeletal organization remain largely unknown. Here we report identification of PSGAP, a novel protein that interacts with PYK2 and FAK and contains multiple domains including a pleckstrin homology domain, a rhoGTPase-activating protein domain, and a Src homology 3 domain. PYK2 interacts with PSGAP Src homology 3 domain via the carboxyl-terminal proline-rich sequence. PSGAP is able to increase GTPase activity of CDC42 and RhoA in vitro and in vivo. Remarkably, PYK2, but not FAK, can activate CDC42 via inhibition of PSGAP-mediated GTP hydrolysis of CDC42. Moreover, PSGAP is localized at cell periphery in fibroblasts in a pleckstrin homology domain-dependent manner. Over expression of PSGAP in fibroblasts results in reorganization of cytoskeletal structures and changes of cellular morphology, which requires rhoGTPase-activating activity. Taken together, our results suggest that PSGAP is a signaling protein essential for PYK2 regulation of cytoskeletal organization via Rho family GTPases.

Original languageEnglish (US)
Pages (from-to)971-983
Number of pages13
JournalJournal of Cell Biology
Volume152
Issue number5
DOIs
StatePublished - Mar 5 2001

Fingerprint

Focal Adhesion Kinase 2
src Homology Domains
GTP Phosphohydrolases
Focal Adhesion Protein-Tyrosine Kinases
Proteins
Fibroblasts
rho GTP-Binding Proteins
Cellular Structures
Guanosine Triphosphate
Proline
Protein-Tyrosine Kinases
rho GTPase-activating protein
platelet protein P47
Hydrolysis

Keywords

  • CDC42
  • Focal adhesion kinase
  • PSGAP
  • Proline-rich tyrosine kinase 2
  • rhoGAP

ASJC Scopus subject areas

  • Cell Biology

Cite this

Regulation of CDC42 GTPase by proline-rich tyrosine kinase 2 interacting with PSGAP, a novel pleckstrin homology and Src homology 3 domain containing rhoGAP protein. / Ren, Xiu Rong; Du, Quansheng; Huang, Yang Zhong; Ao, Shi Zhou; Mei, Lin; Xiong, Wencheng.

In: Journal of Cell Biology, Vol. 152, No. 5, 05.03.2001, p. 971-983.

Research output: Contribution to journalArticle

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abstract = "Proline-rich tyrosine kinase 2 (PYK2), a tyrosine kinase structurally related to focal adhesion kinase (FAK), is implicated in regulating cytoskeletal organization. However, mechanisms by which PYK2 participates in and regulates cytoskeletal organization remain largely unknown. Here we report identification of PSGAP, a novel protein that interacts with PYK2 and FAK and contains multiple domains including a pleckstrin homology domain, a rhoGTPase-activating protein domain, and a Src homology 3 domain. PYK2 interacts with PSGAP Src homology 3 domain via the carboxyl-terminal proline-rich sequence. PSGAP is able to increase GTPase activity of CDC42 and RhoA in vitro and in vivo. Remarkably, PYK2, but not FAK, can activate CDC42 via inhibition of PSGAP-mediated GTP hydrolysis of CDC42. Moreover, PSGAP is localized at cell periphery in fibroblasts in a pleckstrin homology domain-dependent manner. Over expression of PSGAP in fibroblasts results in reorganization of cytoskeletal structures and changes of cellular morphology, which requires rhoGTPase-activating activity. Taken together, our results suggest that PSGAP is a signaling protein essential for PYK2 regulation of cytoskeletal organization via Rho family GTPases.",
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