Mechanism of inhibition of protein kinase C by 14-3-3 isoforms. 14-3-3 isoforms do not have phospholipase A2 activity.

Inactivation of 14-3-3 Protein Exacerbates Cardiac Hypertrophy and Fibrosis through Enhanced Expression of Protein Kinase C .BETA.2 in Experimental Diabetes

“…the cysteine-rich domain. 24) In our study, the blood glucose level did not differ between DN-14-3-3 and NTG mice after STZ injection (Table 1), but the LV tissue expression of PKCb2 was significantly elevated in DN-14-3-3 mice, compared to NTG mice. These results clearly demonstrate that the functional inactivation of 14-3-3 protein in DN-14-3-3 mice augmented the protein expression of PKCb2 in the diabetic myocardium, and thus elevated PKCb2 probably contributes for the exacerbation of diabetes-induced cardiac hypertrophy and fibrosis.…”

“…It is noteworthy that targeted overexpression of PKCb2 in mouse myocardium resulted in LV hypertrophy and fibrosis. 20,21) Earlier reports indicate that 14-3-3 protein interacts with PKC, [22][23][24] where, Aitken et al 23) have shown by in vitro studies that 14-3-3 protein isolated from sheep brain inhibits PKCb2 in addition to other PKC isozymes. Also, overexpression of 14-3-3 protein inhibited the translocation of PKC.…”

“…[22][23][24] Hyperglycemia or diabetes activates diacylglycerol (DAG), which in turn activates PKC, 17,18) where, the level of DAG in the diabetic heart is positively correlated with the level of glucose in blood. 17) Robinson et al 24) have shown by in vitro studies that DAG (40 mM) and phorbol ester (200 nM) in the presence of phosphatidyl serine, overcomes about 60% of the 14-3-3 mediated inhibition of PKC. This may be due to DAG or phorbol ester produces a conformation of PKC which is less susceptible to inhibition by 14-3-3, and more likely that the interaction site of 14-3-3 on PKC is at or near the DAG/phorbol ester binding site, i.e.…”

“…20,21) Moreover, 14-3-3 protein has been shown to bind to many PKC isoforms and inhibit their enzymatic activities 22,23) by directly binding to the cysteine rich domain of PKC. 24) However, the role of PKCb2 in diabetic cardiomyopathy is not studied well. In the present study, we examined the co-relationship between 14-3-3 protein and PKCb2 in the diabetic myocardium.…”

Analysis of dynamic tyrosine phosphoproteome in LFA‐1 triggered migrating t‐cells

“…The 14-3-3 protein identified in this study has been demonstrated to interact and regulate phosphatidylinositol 3-kinase (Bonnefoy-Berard et al, 1995), Tau (Chun et al, 2004;Yuan et al, 2004;Li and Paudel, 2007), 3BP2/SH3BP2 adaptor protein (Foucault et al, 2003) and PKC( ) (Robinson et al, 1994;Kim et al, 2005;Aitken, 2006;Meller et al, 1996), an enzyme crucial for cytoskeletal rearrangements in lymphocyte migration (Volkov et al, 1998(Volkov et al, , 2001). On the basis of these functions and our previous reports (Volkov et al, 1998(Volkov et al, , 2001Fanning et al, 2005;Verma et al, 2008), we surmised that 14-3-3 might also be involved in T-cell migration and selected this protein for further validation.…”