Protein kinase C and F-actin are essential for stimulation of neuronal FAK tyrosine phosphorylation by G-proteins and amyloid beta protein

Chi Zhang, H. Erin Qiu, Grant A. Krafft, William L. Klein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Focal adhesion kinase (FAK) is a protein tyrosine kinase implicated in signal transduction pathways for integrins, neuropeptides, and lysophosphatidic acid. FAK, first discovered in non-neuronal cells, recently has been reported to occur in neurons, where its tyrosine phosphorylation is upregulated by fibronectin and by the Alzheimer's Aβ peptide. The current work has elucidated molecular events leading to tyrosine phosphorylation of FAK in the rat B103 CNS nerve cell line. Activation of receptor-coupled G-proteins by Mas-7 was found to evoke rapid upregulation of FAK tyrosine phosphorylation (Tyr(P)). Upregulation by Mas-7 was blocked by GF109203X, a potent inhibitor of protein kinase C (PKC). Phorbol ester also upregulated FAK-YP, verifying a role for PKC in the transduction cascade. Upregulation of FAK-YP by activation of G-proteins and PKC was dependent upon intact F-actin, as cytochalasin D abolished stimulation by Mas-7 and by phorbol ester. The relatively slow increase in FAK-YP evoked by chronic exposure to Aβ also was abolished by GF109203X and by cytochalasin D. The results show that tyrosine phosphorylation of FAK in neurons is regulated positively by PKC, functioning down-stream from G-proteins through an F-actin-dependent mechanism. The Alzheimer's Aβ peptide is capable of activating elements of this same signal transduction pathway, via membrane events that remain to be determined.

Original languageEnglish (US)
Pages (from-to)185-188
Number of pages4
JournalFEBS Letters
Volume386
Issue number2-3
DOIs
StatePublished - May 20 1996

Keywords

  • Alzheimer's disease
  • Cytoskeleton
  • Focal adhesion kinase
  • G-protein
  • Protein kinase C
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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