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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.

Publication ,  Journal Article
Ren, XR; Du, QS; Huang, YZ; Ao, SZ; Mei, L; Xiong, WC
Published in: J Cell Biol
March 5, 2001

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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Published In

J Cell Biol

DOI

ISSN

0021-9525

Publication Date

March 5, 2001

Volume

152

Issue

5

Start / End Page

971 / 984

Location

United States

Related Subject Headings

  • src Homology Domains
  • rhoA GTP-Binding Protein
  • ran GTP-Binding Protein
  • cdc42 GTP-Binding Protein
  • Two-Hybrid System Techniques
  • Sequence Alignment
  • Protein-Tyrosine Kinases
  • Protein Transport
  • Protein Binding
  • Proline
 

Citation

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Ren, X. R., Du, Q. S., Huang, Y. Z., Ao, S. Z., Mei, L., & Xiong, W. C. (2001). 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. J Cell Biol, 152(5), 971–984. https://doi.org/10.1083/jcb.152.5.971
Ren, X. R., Q. S. Du, Y. Z. Huang, S. Z. Ao, L. Mei, and W. C. Xiong. “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.J Cell Biol 152, no. 5 (March 5, 2001): 971–84. https://doi.org/10.1083/jcb.152.5.971.
Ren, X. R., et al. “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.J Cell Biol, vol. 152, no. 5, Mar. 2001, pp. 971–84. Pubmed, doi:10.1083/jcb.152.5.971.

Published In

J Cell Biol

DOI

ISSN

0021-9525

Publication Date

March 5, 2001

Volume

152

Issue

5

Start / End Page

971 / 984

Location

United States

Related Subject Headings

  • src Homology Domains
  • rhoA GTP-Binding Protein
  • ran GTP-Binding Protein
  • cdc42 GTP-Binding Protein
  • Two-Hybrid System Techniques
  • Sequence Alignment
  • Protein-Tyrosine Kinases
  • Protein Transport
  • Protein Binding
  • Proline