TYROSINE PHOSPHORYLATION-DEPENDENT AND PHOSPHORYLATION-INDEPENDENT ASSOCIATIONS OF PROTEIN-KINASE C-DELTA WITH SRC FAMILY KINASES IN THE RBL-2H3 MAST-CELL LINE - REGULATION OF SRC FAMILY KINASE-ACTIVITY BY PROTEIN-KINASE C-DELTA

Src kinases and protein kinase C (PKC) have been well studied for thei r role in oncogenic and normal cellular processes. Herein we report on a novel regulatory pathway mediated by the interaction of PKC-delta w ith p53/56(Lyn) (Lyn) and with p6o(Src) (Src) that results in the phos phorylation and increased activity of Lyn and Src, In the RBL-2H3 mast cell line, the interaction of PKC-delta with Lyn required the activat ion of the high affinity receptor for IgE (Fc epsilon RI) while the in teraction with Src was constitutive. Increased complex formation of PK C-delta with Lyn or Src led to increased serine phosphorylation and ac tivity of the Src family kinases, Conversely, Lyn was found to phospho rylate Lyn-associated and recombinant PKC-delta in vitro and the tyros ine 52 phosphorylated PKC-delta was recruited to associate with the Ly n SH2 domain. The constitutive association of PKC-delta with Src did n ot result in the tyrosine phosphorylation of PKC-delta prior to or aft er Fc epsilon RI engagement, However in cells over-expressing PKC-delt a, Fc epsilon RI engagement resulted in the dramatic inhibition of Src activity and some inhibition of Lyn activity, Thus, the interaction a nd cross-talk of PKC-delta with Src family kinases suggests a novel an d inter-dependent mechanism for regulation of enzymatic activity that may serve an important role in cellular responses.