Association between v-Src and protein kinase C delta in v-Src-transformed fibroblasts.
In response to the kinase activity of v-Src there is an increase in the membrane association of the novel protein kinase C (PKC) isoform PKC delta (Zang, Q., Frankel, P., and Foster, D. A. (1995) Cell Growth Differ. 6, 1367-1373). We report here that in v-Src-transformed cells PKC delta co-immunoprecipitates with v-Src and is phosphorylated on tyrosine. The tyrosine-phosphorylated PKC delta had reduced enzymatic activity relative to the non-tyrosine-phosphorylated PKC delta from v-Src-transformed cells. The association between Src and PKC delta was dependent upon both an active Src kinase and membrane association. The association between c-Src Y527F and PKC delta was substantially enhanced by mutating a PKC phosphorylation site at Ser-12 in Src to Ala indicating that PKC delta phosphorylation of Src at Ser-12 destabilizes the interaction, possibly in a negative feedback loop. These data demonstrate that upon recruitment of PKC delta to the membrane in v-Src-transformed cells there is the formation of a Src.PKC delta complex in which PKC delta becomes phosphorylated on tyrosine and down-regulated.
Zang
Q
Q
Department of Biological Sciences, Hunter College of the City University of New York, New York, New York 10021, USA.
Lu
Z
Z
Curto
M
M
Barile
N
N
Shalloway
D
D
Foster
D A
DA
D000818:Animals; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D006224:Cricetinae; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D016391:Genes, src; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D051745:Protein Kinase C-delta; D051381:Rats; D015398:Signal Transduction
D007527:Isoenzymes; C497260:Prkcd protein, rat; D011493:Protein Kinase C; D051745:Protein Kinase C-delta