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

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

doi:10.1073/pnas.1633695100

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

Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9470-5. doi: 10.1073/pnas.1633695100. Epub 2003 Jul 24.

Authors

Yuko Kawakami¹, Jiro Kitaura, Libo Yao, Robert W McHenry, Yu Kawakami, Alexandra C Newton, Shin Kang, Roberta M Kato, Michael Leitges, David J Rawlings, Toshiaki Kawakami

Affiliation

¹ Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA. [email protected]

Abstract

Protein kinase C (PKC) and Syk protein tyrosine kinase play critical roles in immune cell activation including that through the high-affinity IgE receptor, FcepsilonRI. 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 PKCbetaI and PKCalpha, respectively, are phosphorylated by Syk in the membrane compartment of FcepsilonRI-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 FcepsilonRI-stimulated mast cells.

Publication types

Research Support, U.S. Gov't, P.H.S.

MeSH terms

Adaptor Proteins, Signal Transducing*
Amino Acid Sequence
Animals
Binding Sites
Bone Marrow Cells / metabolism
COS Cells
Enzyme Activation
Enzyme Precursors / metabolism*
GRB2 Adaptor Protein
Genetic Vectors
Immunoblotting
Intracellular Signaling Peptides and Proteins
Mice
Mitogen-Activated Protein Kinases / metabolism
Models, Biological
Molecular Sequence Data
Peptides / chemistry
Phosphorylation
Protein Isoforms
Protein Kinase C / metabolism*
Protein Kinase C beta
Protein Kinase C-alpha
Protein-Tyrosine Kinases / metabolism*
Proteins / metabolism
Sequence Homology, Amino Acid
Syk Kinase
Tyrosine / chemistry
ras Proteins / metabolism*
src Homology Domains

Substances

Adaptor Proteins, Signal Transducing
Enzyme Precursors
GRB2 Adaptor Protein
Grb2 protein, mouse
Intracellular Signaling Peptides and Proteins
Peptides
Protein Isoforms
Proteins
Tyrosine
Protein-Tyrosine Kinases
Syk Kinase
Syk protein, mouse
Prkca protein, mouse
Protein Kinase C
Protein Kinase C beta
Protein Kinase C-alpha
Mitogen-Activated Protein Kinases
ras Proteins