Isolation of a NCK-associated kinase, PRK2, an SH3-binding protein and potential effector of Rho protein signaling

Lawrence A. Quilliam, Que T. Lambert, Leigh A. Mickelson-Young, John K. Westwick, Andrew B. Sparks, Brian K. Kay, Nancy A. Jenkins, Debra J. Gilbert, Neal G. Copeland, Channing J. Der

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

The NCK adapter protein is comprised of three consecutive Src homology 3 (SH3) protein-protein interaction domains and a C-terminal SH2 domain. Although the association of NCK with activated receptor protein-tyrosine kinases, via its SH2 domain, implicates NCK as a mediator of growth factor- induced signal transduction, little is known about the pathway(s) downstream of NCK recruitment. To identify potential downstream effectors of NCK we screened a bacterial expression library to isolate proteins that bind its SH3 domains. Two molecules were isolated, the Wiskott-Aldrich syndrome protein (WASP, a putative CDC42 effector) and a serine/threonine protein kinase (PRK2, closely related to the putative Rho effector PKN). Using interspecific backcross analysis the Prk2 gene was mapped to mouse chromosome 3. Unlike WASP, which bound the SH3 domains of several signaling proteins, PRK2 specifically bound to the middle SH3 domain of NCK and (weakly) that of phospholipase Cγ. PRK2 also specifically bound to Rho in a GTP-dependent manner and cooperated with Rho family proteins to induce transcriptional activation via the serum response factor. These data suggest that PRK2 may coordinately mediate signal transduction from activated receptor protein- tyrosine kinases and Rho and that NCK may function as an adapter to connect receptor-mediated events to Rho protein signaling.

Original languageEnglish (US)
Pages (from-to)28772-28776
Number of pages5
JournalJournal of Biological Chemistry
Volume271
Issue number46
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Isolation of a NCK-associated kinase, PRK2, an SH3-binding protein and potential effector of Rho protein signaling'. Together they form a unique fingerprint.

  • Cite this

    Quilliam, L. A., Lambert, Q. T., Mickelson-Young, L. A., Westwick, J. K., Sparks, A. B., Kay, B. K., Jenkins, N. A., Gilbert, D. J., Copeland, N. G., & Der, C. J. (1996). Isolation of a NCK-associated kinase, PRK2, an SH3-binding protein and potential effector of Rho protein signaling. Journal of Biological Chemistry, 271(46), 28772-28776. https://doi.org/10.1074/jbc.271.46.28772