Proceedings of the National Academy of Sciences · 2003 · 73 citations · 30 references
Life SciencesBiochemistryImmunologyCell SignalingProtein-protein InteractionsSignal TransductionIge-mediated AllergyImmune Cell SignalingMast Cell ActivationProtein Kinase CascadesReceptor Tyrosine Kinase SignalingSmall Gtpase SignalingCell ActivationExtracellular Signal-regulated Kinase PathwayExtracellular Signal-regulated Kinase SignalingIge Receptor SignalingImmune Cell ActivationRas SignalingRas Signaling PathwaySh2 Domains
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.
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SH2 domains recognize specific phosphopeptide sequences
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