Abstract
Cas-family proteins serve as docking proteins in integrin-mediated signal transduction. The founding member of this family, p130Cas, becomes tyrosine-phosphorylated in response to extracellular stimuli such as integrin-mediated cell adhesion and ligand engagement of receptor tyrosine kinases. Cas proteins are large multidomain molecules that transmit signals as intermediaries through interactions with signaling molecules such as FAK and other tyrosine kinases, as well as tyrosine phosphatases. After Cas is tyrosine-phosphorylated, it acts as a docking protein for binding SH2 domains of Src-family kinases. In order to examine the structural basis for a key step in propagation of signals by Cas, one of the major SH2-binding sites of Cas has been crystallized in complex with the SH3-SH2 regulatory domains of the Src-family kinase Lck. Crystallization conditions were identified by high-throughput screening and optimized with multiple rounds of seeding. The crystals formed at 295 K in space group P2(1)2(1)2(1), with unit-cell parameters a = 77.4, b = 107.3, c = 166.4 A, and diffract to 2.7 A resolution.
References
Nov 7, 1995·Proceedings of the National Academy of Sciences of the United States of America·T R Polte, S K Hanks
Apr 21, 1994·Nature·M J EckS C Harrison
Jun 23, 1995·The Journal of Biological Chemistry·Y NojimaY Yazaki
Sep 22, 1995·The Journal of Biological Chemistry·K Vuori, E Ruoslahti
Apr 12, 1996·The Journal of Biological Chemistry·T NakamotoH Hirai
Jun 1, 1996·Genes & Development·K Alexandropoulos, D Baltimore
Oct 1, 1996·The Journal of Experimental Medicine·M MinegishiC Morimoto
Dec 6, 1996·The Journal of Biological Chemistry·F LiuJ Chernoff
Aug 18, 1997·Oncogene·A J GartonN K Tonks
Aug 1, 1997·European Journal of Immunology·H KandaY Nojima
Apr 16, 1998·The Journal of Biological Chemistry·Y OhashiC Morimoto
Aug 14, 1999·Science·F G Giancotti, E Ruoslahti
Feb 17, 2000·Trends in Cell Biology·G M O'NeillE A Golemis
Apr 30, 2003·Journal of Structural Biology·Joseph R LuftGeorge T DeTitta