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Research Database PMU-SQQUID

Protein kinase C delta induces Src kinase activity via activation of the protein tyrosine phosphatase PTP alpha.
Brandt, DT; Goerke, A; Heuer, M; Gimona, M; Leitges, M; Kremmer, E; Lammers, R; Haller, H; Mischak, H;
J Biol Chem. 2003; 278(36): 34073-34078.
Originalarbeiten (Zeitschrift)

PMU-Authors

Gimona Mario

Abstract

Previously we have shown that protein kinase C (PKC)-mediated reorganization of the actin cytoskeleton in smooth muscle cells is transmitted by the nonreceptor tyrosine kinase, Src. Several authors have described how 12-O- tetradecanoylphorbol-13-acetate(TPA) stimulation of cells results in an increase of Src activity, but the mechanism of the PKC-mediated Src activation is unknown. Using PKC isozymes purified from Spodoptera frugiperda insect cells, we show here that PKC is not able to activate Src directly. Our data reveal that the PKC-dependent Src activation occurs via the activation of the protein tyrosine phosphatase (PTP) PTPalpha. PTPalpha becomes activated in vivo after TPA stimulation. Further, we show that PKCdelta phosphorylates and activates only PTPalpha in vitro but not any other of the TPA-responsive PKC isozymes that are expressed in A7r5 rat aortic smooth muscle cells. To further substantiate our data, we show that cells lacking PKCdelta have a markedly reduced PTPalpha and Src activity after 12-O-tetradecanoylphorbol-13-acetate stimulation. These data support a model in which the main mechanism of 12-O-tetradecanoylphorbol-13- acetate-induced Src activation is the direct phosphorylation and activation of PTPalpha by PKCdelta, which in turn dephosphorylates and activates Src.


Useful keywords (using NLM MeSH Indexing)

Actins/metabolism

Animals

Aorta/cytology

Carcinogens

Cell Line

Cell Membrane/metabolism

Cells, Cultured

Cytoskeleton/metabolism

Enzyme Activation

Fibroblasts/metabolism

Glutathione Transferase/metabolism

Insects

Mice

Mice, Knockout

Models, Biological

Muscle, Skeletal/cytology

Muscle, Smooth/metabolism

Phosphorylation

Plasmids/metabolism

Protein Isoforms

Protein Kinase C/metabolism

Protein Kinase C/physiology*

Protein Kinase C-delta

Protein Tyrosine Phosphatases/metabolism*

Rats

Recombinant Fusion Proteins/metabolism

Tetradecanoylphorbol Acetate

Transfection

src-Family Kinases/metabolism*