ShcA mediates the dominant pathway to extracellular signal-regulated kinase activation during early thymic development.

ABSTRACT: During thymic development, the beta selection checkpoint is regulated by pre-T-cell receptor-initiated signals. Progression through this checkpoint is influenced by phosphorylation and activation of the serine/threonine kinases extracellular signal-regulated kinase 1 (ERK1) and ERK2, but the in vivo relevance of specific upstream players leading to ERK activation is not known. Here, using mice with a conditional loss of the shc1 gene or expressing mutants of ShcA, we demonstrate that the adapter protein ShcA is responsible for up to 70% of ERK activation in double-negative (DN) thymocytes in vivo and ex vivo. We also identify two specific tyrosines on ShcA that promote ERK phosphorylation in vivo, and mice expressing ShcA with mutations of these tyrosines show impaired DN thymocyte develop

SUBMITTER: Trampont P 

PROVIDER: S-EPMC1636838 | biostudies-literature | 2006 Dec

REPOSITORIES: biostudies-literature