Phospho-LAT-independent activation of the Ras-mitogen-activated protein kinase pathway: A differential recruitment model of TCR partial agonist signaling

Stimulation of mature T cells with agonist ligands of the Ag receptor (TCR) causes rapid phosphorylation of tyrosine-based activation motifs in the in tracellular portion of TCR-zeta and CD3 and activation of several intracell ular signaling cascades. Coordinate activation of these pathways is depende nt on Lck- and ZAP-70-mediated tyrosine phosphorylation of a 36-kDa linker for activation of T cells and subsequent recruitment of phospholipase C-gam ma 1, Grb2-SOS, and SLP-76-vav, Here, we show that TCR partial agonist liga nds can selectively activate one of these pathways, the Ras-mitogen-activat ed protein kinase pathway, by inducing recruitment of Grb2-SOS complexes to incompletely phosphorylated p21 phospho-TCR-zeta, This bypasses the need f or activation of Lck and ZAP-70, and for phosphorylation of the linker for activation of T cells to activate Pas, We propose a general model in which differential recruitment of activating complexes away from transmembrane li nker proteins may determine selective activation of a given signaling pathw ay.