Diversity of roles of protein kinase Cα in the proliferation of Swiss 3T3 cells

Author:

FLORIN-CHRISTENSEN Jorge1,FLORIN-CHRISTENSEN Monica1,MEINARDI Elsa2,CALLE R3

Affiliation:

1. Institute of Neuroscience, Ciudad Universitaria, Pab II, 4 °Piso, 1428 Buenos Aires, Argentina

2. Department of Cell Biology, Ciudad Universitaria, Pab II, 4 °Piso, 1428 Buenos Aires, Argentina

3. Institute for Molecular Medicine and Genetics, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912-3175, U.S.A.

Abstract

We examined the role of protein kinase Cα (PKCα) in the stimulation of DNA synthesis of Swiss 3T3 cells induced by bombesin, platelet-derived growth factor (PDGF) and phorbol 12-myristate 13-acetate (PMA). We found that cells in which this kinase had been down-regulated showed a partially abrogated mitogenic response to bombesin. The response to PDGF was unaltered; however, the response to PMA was completely suppressed. The mitogenic effect of maximal doses of bombesin and PMA combined was greater than that of either agent alone, suggesting that bombesin does not fully activate the PKC pathway. Accordingly, bombesin-induced PKCα translocation from cytosol to membranes was partial, while that observed with PMA was essentially complete. Moreover, exposure to Ro-31-8220, a PKC inhibitor, had signficantly greater effects on the response to PMA than on that to bombesin. Our findings point out different roles that PKCα may play in diversely activated cells: while, in the case of PMA, stimulation of this kinase may be necessary and sufficient to induce proliferation, it appears to be necessary only for a full response to bombesin, and redundant among the mechanisms triggered by PDGF.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry

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