14-3-3Gamma interacts with and is phosphorylated by multiple protein kinase C isoforms in PDGF-stimulated human vascular smooth muscle cells.
It has recently been demonstrated that some members of the 14-3-3 protein family play an important role in signal transduction leading to cellular proliferation. We have previously shown that expression of 14-3-3gamma is induced by growth factors in human vascular smooth muscle cells (VSMC). In this study, we cloned the human homolog of 14-3-3gamma and observed many potential phosphorylation sites, suggesting the potential for post-translational modification. In VSMC treated with platelet-derived growth factor (PDGF), 14-3-3gamma protein was expressed and phosphorylated in an activation-dependent manner. Platelet-derived growth factor-induced phosphorylation could be inhibited by phosphokinase C (PKC) inhibitory compounds, and 14-3-3gamma could be phosphorylated in the absence of PDGF by compounds that activate PKC. We also demonstrated interaction between 14-3-3gamma and several PKC isoforms (alpha, beta, gamma, theta, and delta), implicating these PKC family isoforms as the kinases responsible for PDGF-induced 14-3-3gamma phosphorylation. We found that 14-3-3gamma interacted with the signal transduction protein Raf-1, suggesting that 14-3-3gamma provides a link between this protein and PKC. Thus, 14-3-3gamma may represent a signal transduction protein that is regulated transcriptionally and post-transcriptionally by growth factors.
Autieri
M V
MV
Department of Cardiology and Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA. mautieri@unix.temple.edu
Carbone
C J
CJ
D048948:14-3-3 Proteins; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011233:Precipitin Tests; D020033:Protein Isoforms / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase
D048948:14-3-3 Proteins; D010982:Platelet-Derived Growth Factor; D020033:Protein Isoforms; D011506:Proteins; D014446:Tyrosine 3-Monooxygenase; D011493:Protein Kinase C