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

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.

authors

Kawakami Y,Kitaura J,Yao L,McHenry RW,Kawakami Y,Newton AC,Kang S,Kato RM,Leitges M,Rawlings DJ,Kawakami T

doi

10.1073/pnas.1633695100

keywords:

subject

Has Abstract

pub_date

2003-08-05 00:00:00

pages

9470-5

issue

16

eissn

0027-8424

issn

1091-6490

pii

1633695100

journal_volume

100

pub_type

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