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
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3T3 Cells
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Animals
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Benzylamines / pharmacology
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Calcium / metabolism
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Dose-Response Relationship, Drug
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Egtazic Acid / analogs & derivatives
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Egtazic Acid / pharmacology
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Guanine Nucleotide Exchange Factors
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Indoles / pharmacology
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Isoenzymes / metabolism*
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Mice
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Phospholipase C gamma
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Phosphorylation
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Platelet-Derived Growth Factor / pharmacology*
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism*
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Proteins / metabolism*
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Signal Transduction
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Substrate Specificity
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Sulfonamides / pharmacology
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T-Lymphoma Invasion and Metastasis-inducing Protein 1
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Threonine / metabolism
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Type C Phospholipases / metabolism*
Substances
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Benzylamines
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Guanine Nucleotide Exchange Factors
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Indoles
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Isoenzymes
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Platelet-Derived Growth Factor
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Proteins
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Sulfonamides
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T-Lymphoma Invasion and Metastasis-inducing Protein 1
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Tiam1 protein, mouse
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KN 93
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1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
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Threonine
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Egtazic Acid
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Protein Kinase C
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases
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Type C Phospholipases
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Phospholipase C gamma
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Calcium
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Ro 31-8220