Cbl enforces an SLP76-dependent signaling pathway for T cell differentiation.

ABSTRACT: A signaling pathway involving ZAP-70, LAT, and SLP76 has been regarded as essential for receptor-driven T cell development and activation. Consistent with this model, mice deficient in SLP76 have a complete block at the double negative 3 stage of T cell development. Recently, however, it has been reported that inactivation of Cbl, a ubiquitin-protein isopeptide ligase, partially rescues T cell development in SLP76-deficient mice. To probe the influence of Cbl on domain-specific SLP76 functions, we reconstituted SLP76(-/-) Cbl(-/-) mice with Slp76 transgenes bearing mutations in each of three functional domains of SLP76 as follows: Y3F, in which the amino-terminal tyrosine residues of SLP76 were mutated, eliminating sites of SLP76 interaction with Vav, Nck, and Itk; Delta20, in which 20 ami

SUBMITTER: Chiang YJ 

PROVIDER: S-EPMC2640981 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature