The role of p21ras in CD28 signal transduction: triggering of CD28 with antibodies, but not the ligand B7-1, activates p21ras.

• DOI: 10.1084/jem.180.3.1067
• Publication Date: 2004-06-24T07:56:10Z
• Authors: J A Nunès; Y Collette; A Truneh; D Olive; D A Cantrell
• Keywords: GRB2

CD28 is a 44-kD homodimer expressed on the surface of majority human T cells that provides an important costimulus for cell activation. The biochemical basis accessory signals poorly understood. Triggering antigen receptor (TCR) activates p21ras proteins. Here we show ligation by monoclonal antibody (mAb) also stimulates and induces Ras-dependent events such as stimulation microtubule-associated protein (MAP) kinase ERK2 hyperphosphorylation Raf-1. One physiological ligand molecule B7-1. In contrast to effect mAb, present studies interactions between B7-1 do not stimulate signaling pathways. Two substrates TCR-regulated tyrosine kinases (PTKs) have been implicated in activation cells: p95vav 36-kD associates with complex Grb2 Ras exchange Sos. both antibodies cellular PTKs, exploited differences attempt identify critical PTK-controlled cells. data against TCR or induce phosphorylation Vav p36. but has no apparent Grb2-associated p36 protein. intensity greater than TCR-stimulated Moreover kinetics prolonged B7-1-stimulated These signaling, correlates more closely phosphorylation. However, experiments demonstrate major substrate B7-activated PTKs hence could be signal transduction pathway.