Protein kinase D1 and the β1 integrin cytoplasmic domain control β1 integrin function via regulation of Rap1 activation

Ricardo B. Medeiros, Deborah M. Dickey, Heekyoung Chung, Angie C. Quale, Lakshmi R. Nagarajan, Daniel D. Billadeau, Yoji Shimizu

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

The functional activity of integrins is dynamically regulated by T cell receptor stimulation and by protein kinase C (PKC). We report a novel function for the PKC effector protein kinase D1 (PKD1) in integrin activation. Constitutively active and kinase-inactive PKD1 mutants lacking the PKD1 pleckstrin homology (PH) domain block phorbol ester- and TCR-mediated activation and clustering of β1 integrins. The PH domain of PKD1 mediates the association of PKD1 with the GTPase Rap1 and is central to Rap1 activation and membrane translocation in T cells. Furthermore, PKD1 and Rap1 associate with β1 integrins in a manner that is dependent on the carboxy-terminal end of the β1 integrin subunit cytoplasmic domain. β1 integrin expression is required for Rap1 activation and membrane localization of the PKD1-Rap1 complex. Therefore, PKD1 promotes integrin activation in T cells by regulating Rap1 activation and membrane translocation via interactions with the β1 integrin subunit cytoplasmic domain.

Original languageEnglish (US)
Pages (from-to)213-226
Number of pages14
JournalImmunity
Volume23
Issue number2
DOIs
StatePublished - Aug 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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