BACKGROUND: Leukocyte activation results in a rapid increase in adhesion to the extracellular matrix due to the activation of @entity2393 receptors. A role for @entity4357 (PI) 3-kinase in integrin activation has been proposed, as activation of integrins by many receptors can be blocked by PI 3-kinase inhibitors. One receptor that regulates integrins is the @entity1361 surface antigen; here, we investigated the mechanisms responsible for @entity1361 -mediated integrin activation. RESULTS: @entity1361 -mediated integrin activation was blocked by mutation of the binding site for the @entity8569 catalytic subunit of PI 3-kinase in the @entity1361 cytoplasmic domain, and by expression of a dominant-negative form of the @entity8569 subunit. Substitution of the Src homology 2 (SH2)-binding motif in the @entity1361 cytoplasmic domain for the corresponding motif in the @entity1361 -related @entity4386 surface antigen also blocked integrin activation but did not affect the recruitment and activation of PI 3-kinase. Mutations of the @entity1361 cytoplasmic domain that blocked integrin activation also impaired the @entity669 phosphorylation of the @entity5315 adaptor protein and the activation of the PI 3-kinase that was associated with @entity5315 . This @entity5315 -associated PI 3-kinase was distinct from the PI 3-kinase that coprecipitated with the @entity1361 cytoplasmic domain. @entity1361 -mediated activation of @entity2393 was inhibited by expression of a mutant @entity5315 protein that shows reduced association with PI 3-kinase. CONCLUSIONS: @entity5315 is required for PI-3-kinase-dependent regulation of integrin receptors by @entity1361 . Furthermore, @entity1361 is coupled to two distinct pools of PI 3-kinase, one directly associated with the @entity1361 cytoplasmic tail and the other associated with @entity5315 .

Regulation of @entity2393 -mediated cell adhesion by the XXXX adaptor protein.

@entity4357 :: ('MESH:D010716', 'Chemical') :: ['phosphatidylinositol'] @entity1361 :: ('940', 'Gene') :: ['CD28'] @entity5315 :: ('867', 'Gene') :: ['Cbl'] @entity2393 :: ('3688', 'Gene') :: ['beta 1 integrin', 'beta 1 integrins'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine'] @entity4386 :: ('1493', 'Gene') :: ['CTLA-4'] @entity8569 :: ('5296', 'Gene') :: ['p85']
@entity5315 :: (867,Gene) :: ['Cbl']
