ADAP-ting TCR Signaling to Integrins
Emily K. Griffiths1,2 and
Josef M. Penninger1,2*
1Amgen, Departments of Medical Biophysics and Immunology, University of Toronto, 620 University Avenue, Toronto, Ontario, Canada M5G 2C1.
2Institute for Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 7, A-1030 Vienna, Austria.
Abstract:
Adaptor proteins are essential components of T cell receptor (TCR) signaling cascades regulating gene transcription and cytoskeletal reorganization. The molecular adaptor adhesion- and degranulation-promoting adaptor protein (ADAP), also known as Fyn binding protein (FYB) or Slp-76-associated protein of 130 kilodaltons (SLAP-130), interacts with a number of signaling intermediates including Slp-76, the Src family tyrosine kinase Fyn, vasodilator-stimulated phosphoprotein (VASP), and the actin-nucleating protein WASP. Recently ADAP was shown genetically to positively regulate T cell activation, TCR-induced integrin clustering, and T cell adhesion. The mechanism by which ADAP couples TCR stimulation to integrin clustering remains unclear; however, studies of ADAP, the exchange factor Vav1, and WASP suggest that TCR and integrin clustering may be controlled by distinct signaling pathways.
*Corresponding author. Telephone, 416-204-2244; fax, 416-204-2278; e-mail, jpenning{at}amgen.com
