Tyrosine phosphorylation-dependent and -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

Oncogene. 1998 Jul 2;16(26):3357-68. doi: 10.1038/sj.onc.1201886.


Src kinases and protein kinase C (PKC) have been well studied for their role in oncogenic and normal cellular processes. Herein we report on a novel regulatory pathway mediated by the interaction of PKC-delta with p53/56Lsy (Lyn) and with p60Src (Src) that results in the phosphorylation and increased activity of Lyn and Src. In the RBL-2H3 mast cell line, the interaction of PKC-delta with Lyn required the activation of the high affinity receptor for IgE (FcsigmaRI) while the interaction with Src was constitutive. Increased complex formation of PKC-delta with Lyn or Src led to increased serine phosphorylation and activity of the Src family kinases. Conversely, Lyn was found to phosphorylate Lyn-associated and recombinant PKC-delta in vitro and the tyrosine 52 phosphorylated PKC-delta was recruited to associate with the Lyn SH2 domain. The constitutive association of PKC-delta with Src did not result in the tyrosine phosphorylation of PKC-delta prior to or after FsigmaRI engagement. However in cells over-expressing PKC-delta, FsigmaRI engagement resulted in the dramatic inhibition of Src activity and some inhibition of Lyn activity. Thus, the interaction and cross-talk of PKC-delta with Src family kinases suggests a novel and inter-dependent mechanism for regulation of enzymatic activity that may serve an important role in cellular responses.

MeSH terms

  • Animals
  • Biological Transport
  • Gene Expression Regulation, Enzymologic
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Mast Cells / enzymology*
  • Membrane Proteins / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Protein Kinase C-delta
  • Proto-Oncogene Proteins pp60(c-src) / metabolism
  • Rats
  • Receptors, IgE / metabolism
  • Recombinant Proteins / metabolism
  • Tumor Cells, Cultured
  • Tyrosine / metabolism
  • Vanadates / pharmacology
  • src-Family Kinases / metabolism*


  • Isoenzymes
  • Membrane Proteins
  • Receptors, IgE
  • Recombinant Proteins
  • pervanadate
  • Vanadates
  • Tyrosine
  • Prkcd protein, rat
  • Proto-Oncogene Proteins pp60(c-src)
  • lyn protein-tyrosine kinase
  • src-Family Kinases
  • Protein Kinase C
  • Protein Kinase C-delta