Diversity of roles of protein kinase C alpha in the proliferation of Swiss 3T3 cells .

Florin-Christensen J ; Florin-Christensen M ; Meinardi E ; Calle R

Institute of Neuroscience , Ciudad Universitaria , Buenos Aires , Argentina .

Biochem J 315 ( Pt 2 ) : 513-6 ( 1996)

Abstract
We examined the role of protein kinase C alpha ( PKC alpha ) in the stimulation of DNA synthesis of Swiss 3T3 cells induced by bombesin , platelet-derived growth factor ( PDGF ) and phorbol 12-myristate -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 PKC alpha 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 significantly greater effects on the response to PMA than on that to bombesin . Our findings point out different roles that PKC alpha 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 .