Integrin-mediated Tyrosine Phosphorylation of Shc in T Cells Is Regulated by Protein Kinase C-dependent Phosphorylations of Lck

AUTOR(ES)

Niu, Shi

FONTE

The American Society for Cell Biology

RESUMO

Integrin receptor signals are costimulatory for mitogenesis with the T-cell receptor during T-cell activation. A subset of integrin receptors can link to the adapter protein Shc and provide a mitogenic stimulus. Using a combination of genetic and pharmacological approaches, we show herein that integrin signaling to Shc in T cells requires the receptor tyrosine phosphatase CD45, the Src family kinase member Lck, and protein kinase C. Our results suggest a model in which integrin-dependent serine phosphorylation of Lck is the critical step that determines the efficiency of Shc tyrosine phosphorylation in T cells. Serine phosphorylation of Lck is dependent on PKC and is also linked to CD45 dephosphorylation. Mutants of Lck that cannot be phosphorylated on the critical serine residues do not signal efficiently to Shc and have greatly reduced kinase activity. This signaling from integrins to Lck may be an important step in the costimulation with the T-cell receptor during lymphocyte activation.

Documentos Relacionados

• Mitogenic Response of Murine B Lymphocytes to Salmonella typhimurium Lipopolysaccharide Requires Protein Kinase C-Dependent Late Tyrosine Phosphorylations
• Cofilin Phosphorylation by Protein Kinase Testicular Protein Kinase 1 and Its Role in Integrin-mediated Actin Reorganization and Focal Adhesion Formation
• Integrin-mediated Signaling Events in Human Endothelial Cells
• Dioxin-dependent activation of murine Cyp1a-1 gene transcription requires protein kinase C-dependent phosphorylation.
• Protein kinase D (PKD) activation in intact cells through a protein kinase C-dependent signal transduction pathway.