ARAP, a Novel Adaptor Protein, Is Required for TCR Signaling and Integrin-Mediated Adhesion

Abstract

A novel adaptor protein was identified by analyzing phosphotyrosine proteomes from membrane rafts of activated T cells. This protein showed sequence similarity to a well-known T cell adaptor protein, adhesion and degranulation-promoting adaptor protein (ADAP); therefore, the novel protein was designated activation-dependent, raft-recruited ADAP-like phosphoprotein (ARAP). Suppression of ARAP impaired the major signaling pathways downstream of the TCR. ARAP associated with the Src homology 2 domain of Src homology 2-containing leukocyte protein of 76 kDa via the phosphorylation of two YDDV motifs in response to TCR stimulation. ARAP also mediated integrin activation but was not involved in actin polymerization. The results of this study indicate that a novel T cell adaptor protein, ARAP, plays a unique role in T cells as a part of both the proximal activation signaling and inside-out signaling pathways that result in integrin activation and T cell adhesion.