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

I N Fleming, C M Elliott, J H Exton

Research output: Contribution to journalArticle

35 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)229-33
Number of pages5
JournalFEBS Letters
Volume429
Issue number3
Publication statusPublished - 1998

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Phospholipase C gamma
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Phosphorylation
Platelet-Derived Growth Factor
Protein Kinase C
Fibroblasts
Phosphoinositide Phospholipase C
Guanine Nucleotide Exchange Factors
Protein C Inhibitor
Threonine
Protein Kinase Inhibitors
Chelating Agents

Keywords

  • 3T3 Cells
  • Animals
  • Benzylamines
  • Calcium
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Dose-Response Relationship, Drug
  • Egtazic Acid
  • Guanine Nucleotide Exchange Factors
  • Indoles
  • Isoenzymes
  • Mice
  • Phospholipase C gamma
  • Phosphorylation
  • Platelet-Derived Growth Factor
  • Protein Kinase C
  • Proteins
  • Signal Transduction
  • Substrate Specificity
  • Sulfonamides
  • Threonine
  • Type C Phospholipases

Cite this

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title = "Phospholipase C-gamma, protein kinase C and Ca2+/calmodulin-dependent protein kinase II are involved in platelet-derived growth factor-induced phosphorylation of Tiam1",
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.",
keywords = "3T3 Cells, Animals, Benzylamines, Calcium, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Calcium-Calmodulin-Dependent Protein Kinases, Dose-Response Relationship, Drug, Egtazic Acid, Guanine Nucleotide Exchange Factors, Indoles, Isoenzymes, Mice, Phospholipase C gamma, Phosphorylation, Platelet-Derived Growth Factor, Protein Kinase C, Proteins, Signal Transduction, Substrate Specificity, Sulfonamides, Threonine, Type C Phospholipases",
author = "Fleming, {I N} and Elliott, {C M} and Exton, {J H}",
year = "1998",
language = "English",
volume = "429",
pages = "229--33",
journal = "FEBS Letters",
issn = "0014-5793",
publisher = "Elsevier",
number = "3",

}

TY - JOUR

T1 - Phospholipase C-gamma, protein kinase C and Ca2+/calmodulin-dependent protein kinase II are involved in platelet-derived growth factor-induced phosphorylation of Tiam1

AU - Fleming, I N

AU - Elliott, C M

AU - Exton, J H

PY - 1998

Y1 - 1998

N2 - 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.

AB - 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.

KW - 3T3 Cells

KW - Animals

KW - Benzylamines

KW - Calcium

KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2

KW - Calcium-Calmodulin-Dependent Protein Kinases

KW - Dose-Response Relationship, Drug

KW - Egtazic Acid

KW - Guanine Nucleotide Exchange Factors

KW - Indoles

KW - Isoenzymes

KW - Mice

KW - Phospholipase C gamma

KW - Phosphorylation

KW - Platelet-Derived Growth Factor

KW - Protein Kinase C

KW - Proteins

KW - Signal Transduction

KW - Substrate Specificity

KW - Sulfonamides

KW - Threonine

KW - Type C Phospholipases

M3 - Article

C2 - 9662423

VL - 429

SP - 229

EP - 233

JO - FEBS Letters

JF - FEBS Letters

SN - 0014-5793

IS - 3

ER -