A Ras activation pathway dependent on Syk phosphorylation of protein kinase C

• DOI: 10.1073/pnas.1633695100
• Publication Date: 2003-08-05T17:14:48Z
• Authors: Yuko Kawakami; Jiro Kitaura; Libo Yao; Robert W. McHenry; Yu Kawakami; Alexandra C. Newton; Shin Kang; Roberta M. Kato; Michael Leitges; David J. Rawlings; Toshiaki Kawakami
• Keywords: Enzyme Precursors; 0303 health sciences; Binding Sites; Genetic Vectors; Immunoblotting; Molecular Sequence Data; Intracellular Signaling Peptides and Proteins; Bone Marrow Cells; Models, Biological; Enzyme Activation; Mice; 03 medical and health sciences; COS Cells; Animals; Protein Isoforms; Amino Acid Sequence; Mitogen-Activated Protein Kinases; Phosphorylation; Peptides; Protein Kinase C; Adaptor Proteins, Signal Transducing; GRB2 Adaptor Protein

Protein kinase C (PKC) and Syk protein tyrosine kinase play critical roles in immune cell activation including that through the high-affinity IgE receptor, FcεRI. Mechanisms by which PKC activation leads to the activation of Ras, a family of GTPases essential for immune cell activation, have been elusive. We present evidence that Tyr-662 and Tyr-658 of PKCβI and PKCα, respectively, are phosphorylated by Syk in the membrane compartment of FcεRI-stimulated mast cells. These phosphorylations require prior PKC autophosphorylation of the adjacent serine residues (Ser-661 and Ser-657, respectively) and generate a binding site for the SH2 domain of the adaptor protein Grb-2. By recruiting the Grb-2/Sos complex to the plasma membrane, these conventional PKC isoforms contribute to the full activation of the Ras/extracellular signal-regulated kinase signaling pathway in FcεRI-stimulated mast cells.