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Articles by S. F. Steinberg
Total Records ( 1 ) for S. F. Steinberg
  J Guo , L Cong , V. O Rybin , Z Gertsberg and S. F. Steinberg
 

Protein kinase C- (PKC) exerts important cardiac actions as a lipid-regulated kinase. There is limited evidence that PKC also might exert an additional kinase-independent action as a regulator of the subcellular compartmentalization of binding partners such as Shc (Src homologous and collagen), a family of adapter proteins that play key roles in growth regulation and oxidative stress responses. This study shows that native PKC forms complexes with endogenous Shc proteins in H2O2-treated cardiomyocytes; H2O2 treatment also leads to the accumulation of PKC and Shc in a detergent-insoluble cytoskeletal fraction and in mitochondria. H2O2-dependent recruitment of Shc isoforms to cytoskeletal and mitochondrial fractions is amplified by wild-type-PKC overexpression, consistent with the notion that PKC acts as a signal-regulated scaffold to anchor Shc in specific subcellular compartments. However, overexpression studies with kinase-dead (KD)-PKC-K376R (an ATP-binding mutant of PKC that lacks catalytic activity) are less informative, since KD-PKC-K376R aberrantly localizes as a constitutively tyrosine-phosphorylated enzyme to detergent-insoluble and mitochondrial fractions of resting cardiomyocytes; relatively little KD-PKC-K376R remains in the cytosolic fraction. The aberrant localization and tyrosine phosphorylation patterns for KD-PKC-K376R do not phenocopy the properties of native PKC, even in cells chronically treated with GF109203X to inhibit PKC activity. Hence, while KD-PKC-K376R overexpression increases Shc localization to the detergent-insoluble and mitochondrial fractions, the significance of these results is uncertain. Our studies suggest that experiments using KD-PKC-K376R overexpression as a strategy to competitively inhibit the kinase-dependent actions of native PKC or to expose the kinase-independent scaffolding functions of PKC should be interpreted with caution.

 
 
 
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