Sci. STKE, 3 February 2004
CELL ADHESION Controlling Distribution by Cleavage
Arachidonic acid (AA) stimulates the adhesion of cells, such as the metastatic breast carcinoma cell line MDA-MB-435, to extracellular matrix proteins, such as collagen. Kennett et al. show that exposure of cells to AA stimulates activation of protein kinase Cμ (PKCμ) and the p38 mitogen-activated protein kinase and promotes adhesion of MDA-MB-435 to collagen. Not only was PKCμ activated by phosphorylation in response to AA, it was translocated to the membrane and cleaved by calpain, which resulted in the accumulation of a truncated, activated cytosolic form of PKCμ. Pharmacological inhibition of PKCμ or calpain decreased cell adhesion in response to AA. Stimulation of phosphorylation of PKCμ or p38 was independent of each other, on the basis of pharmacological inhibition experiments. However, inhibition of p38 activity did decrease the calpain-mediated proteolysis of PKCμ. Thus, p38 may provide feedback on the PKCμ arm of the pathway not at the level of activation, but at the level of proteolysis by calpain and subsequent subcellular redistribution of the truncated active form of PKCμ.
S. B. Kennett, J. D. Roberts, K. Olden, Requirement of protein kinase Cμ activation and calpain-mediated proteolysis for arachidonic acid-stimulated adhesion of MDA-MB-435 human mammary carcinoma cells to collagen type IV. J. Biol. Chem. 279, 3300-3307 (2004). [Abstract] [Full Text]
Citation: Controlling Distribution by Cleavage. Sci. STKE 2004, tw44 (2004).
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