Protein Kinase Cδ Induces Src Kinase Activity via Activation of the Protein Tyrosine Phosphatase PTPα*

By Dominique T Brandt, Axel Goerke, M. Heuer, M. Gimona, M. Leitges, E. Kremmer, R. Lammers, H. Haller, H. Mischak. Journal of Biological Chemistry, 2003

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Previously we have shown that protein kinase C (PKC)-mediated reorganization of the actin cytoskeleton in smooth muscle cells is transmitted by the non-receptor 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) PTPα. PTPα becomes activated in vivo after TPA stimulation. Further, we show that PKCδ phosphorylates and activates only PTPα 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 PKCδ have a markedly reduced PTPα 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 PTPα by PKCδ, which in turn dephosphorylates and activates Src.

Subfields: Cardiology and Cardiovascular Medicine, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9f030a99bd4e4b6540f987b92a21530f4353868a