Phospholipase C-gamma, protein kinase C and Ca2+/calmodulin-dependent protein kinase II are involved in platelet-derived growth factor-induced phosphorylation of Tiam1

FEBS Lett. 1998 Jun 16;429(3):229-33. doi: 10.1016/s0014-5793(98)00566-3.

Abstract

In Swiss 3T3 fibroblasts, the Rac1-specific guanine nucleotide exchange factor Tiam1 is phosphorylated by several different agonists. We show here that PDGF induces threonine phosphorylation of Tiam1 in a time- and dose-dependent manner. Tiam1 phosphorylation was significantly reduced by the selective protein kinase C inhibitor Ro-31-8220 and by KN93, an inhibitor of Ca2+/calmodulin-dependent protein kinase II. The Ca2+ chelator BAPTA/AM totally abrogated Tiam1 phosphorylation, indicating that Ca2+ is essential for this phosphorylation. Moreover, PDGF-stimulated Tiam1 phosphorylation was markedly reduced by 72 +/- 10% in PLC-gamma1 deficient mouse fibroblasts, compared to wild-type cells, indicating that phosphoinositide phospholipase C is involved.

MeSH terms

  • 3T3 Cells
  • Animals
  • Benzylamines / pharmacology
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Dose-Response Relationship, Drug
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Guanine Nucleotide Exchange Factors
  • Indoles / pharmacology
  • Isoenzymes / metabolism*
  • Mice
  • Phospholipase C gamma
  • Phosphorylation
  • Platelet-Derived Growth Factor / pharmacology*
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Proteins / metabolism*
  • Signal Transduction
  • Substrate Specificity
  • Sulfonamides / pharmacology
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1
  • Threonine / metabolism
  • Type C Phospholipases / metabolism*

Substances

  • Benzylamines
  • Guanine Nucleotide Exchange Factors
  • Indoles
  • Isoenzymes
  • Platelet-Derived Growth Factor
  • Proteins
  • Sulfonamides
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1
  • Tiam1 protein, mouse
  • KN 93
  • 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • Threonine
  • Egtazic Acid
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Type C Phospholipases
  • Phospholipase C gamma
  • Calcium
  • Ro 31-8220