14-3-3 gamma 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 f amily play an important role in signal transduction leading to cellular pro liferation. We have previously shown that expression of 14-3-3 gamma is ind uced by growth factors in human vascular smooth muscle cells (VSMC), In thi s study, we cloned the human homolog of 14-3-3 gamma and observed many pote ntial phosphorylation sites, suggesting the potential for posttranslational modification. In VSMC treated with platelet-derived growth factor (PDGF), 14-3-3 gamma protein was expressed and phosphorylated in an activation-depe ndent manner. Platelet-derived growth factor-induced phosphorylation could be inhibited by phosphokinase C (PKC) inhibitory compounds, and 14-3-3 gamm a could be phosphorylated in the absence of PDGF by compounds that activate PKC, We also demonstrated interaction between 14-3-3 gamma and several PKC isoforms (alpha, beta, gamma, theta, and delta), implicating these PKC fam ily isoforms as the kinases responsible for PDGF-induced 14-3-3 gamma phosp horylation, We found that 14-3-3 gamma interacted with the signal transduct ion protein Raf-1, suggesting that 14-3-3 gamma provides a link between thi s protein and PKC, Thus, 14-3-3 gamma may represent a signal transduction p rotein that is regulated transcriptionally and post-transcriptionally by gr owth factors.