First Author | de Souza AJ | Year | 2008 |
Journal | J Immunol | Volume | 180 |
Issue | 10 | Pages | 6518-26 |
PubMed ID | 18453570 | Mgi Jnum | J:134962 |
Mgi Id | MGI:3790155 | Doi | 10.4049/jimmunol.180.10.6518 |
Citation | de Souza AJ, et al. (2008) T cell Ig and mucin domain-1-mediated T cell activation requires recruitment and activation of phosphoinositide 3-kinase. J Immunol 180(10):6518-26 |
abstractText | Ligation of the transmembrane protein T cell Ig and mucin domain (Tim)-1 can costimulate T cell activation. Agonistic Abs to Tim-1 are also capable of inducing T cell activation without additional stimuli. However, little is known about the biochemical mechanisms underlying T cell stimulation or costimulation through Tim-1. We show that a tyrosine in Tim-1 becomes phosphorylated in a lck-dependent manner, whereupon it can directly recruit p85 adaptor subunits of PI3K. This results in PI3K activation, which is required for Tim-1 function. We also provide genetic evidence that p85 expression is required for optimal Tim-1 function. Thus, we describe a pathway from Tim-1 tyrosine phosphorylation to the PI3K signaling pathway, which appears to be a major effector of Tim-1-mediated T cell activation. |