Signal transduction by the platelet integrin alpha IIb beta 3: induction of calcium oscillations required for protein-tyrosine phosphorylation and ligand-induced spreading of stably transfected cells

AJ Pelletier, SC Bodary and AD Levinson

Genentech Inc., South San Francisco, California 94080.

We demonstrate an example of signal transduction by an integrin and have begun to define the pathway through which this signaling is achieved. We constructed a stably transfected derivative of 293 cells (ATCC 1573) that expresses the platelet integrin GPIIbIIIa (alpha IIb beta 3). This cell line, clone B, adheres to and spreads on fibrinogen, a ligand for alpha IIb beta 3, while the parent cell line does not. Stimulation of these cells either by adhesion to fibrinogen or with antiserum directed against alpha IIb beta 3 results in induction of calcium oscillations, followed by tyrosine phosphorylation of at least one protein of molecular weight approximately 125 kDa. We establish that this phosphorylation, as well as the morphological rearrangements, requires the mobilization of calcium.

Volume 3, Issue 9, pp. 989-998, 09/01/1992
Copyright © 1992 by The American Society for Cell Biology

This article has been cited by other articles:

				G. R. Van de Walle, A. Schoolmeester, B. F. Iserbyt, J. M. E. M. Cosemans, J. W. M. Heemskerk, M. F. Hoylaerts, A. Nurden, K. Vanhoorelbeke, and H. Deckmyn Activation of {alpha}IIb{beta}3 is a sufficient but also an imperative prerequisite for activation of {alpha}2{beta}1 on platelets Blood, January 15, 2007; 109(2): 595 - 602. [Abstract] [Full Text] [PDF]

				A. D. Doyle and J. Lee Cyclic changes in keratocyte speed and traction stress arise from Ca2+-dependent regulation of cell adhesiveness J. Cell Sci., January 15, 2005; 118(2): 369 - 379. [Abstract] [Full Text] [PDF]

				A. Doyle, W. Marganski, and J. Lee Calcium transients induce spatially coordinated increases in traction force during the movement of fish keratocytes J. Cell Sci., May 1, 2004; 117(11): 2203 - 2214. [Abstract] [Full Text] [PDF]

				X. Xi, R. J. Bodnar, Z. Li, S. C.-T. Lam, and X. Du Critical roles for the COOH-terminal NITY and RGT sequences of the integrin {beta}3 cytoplasmic domain in inside-out and outside-in signaling J. Cell Biol., July 21, 2003; 162(2): 329 - 339. [Abstract] [Full Text] [PDF]

				D. D. Hu, C. A. White, S. Panzer-Knodle, J. D. Page, N. Nicholson, and J. W. Smith A New Model of Dual Interacting Ligand Binding Sites on Integrin alpha IIbbeta 3 J. Biol. Chem., February 19, 1999; 274(8): 4633 - 4639. [Abstract] [Full Text] [PDF]

				L. S. Price, J. Leng, M. A. Schwartz, and G. M. Bokoch Activation of Rac and Cdc42 by Integrins Mediates Cell Spreading Mol. Biol. Cell, July 1, 1998; 9(7): 1863 - 1871. [Abstract] [Full Text]

				C. Zheng, Z. Xing, Z. C. Bian, C. Guo, A. Akbay, L. Warner, and J.-L. Guan Differential Regulation of Pyk2 and Focal Adhesion Kinase (FAK). THE C-TERMINAL DOMAIN OF FAK CONFERS RESPONSE TO CELL ADHESION J. Biol. Chem., January 23, 1998; 273(4): 2384 - 2389. [Abstract] [Full Text] [PDF]

				M. Rusnati, E. Tanghetti, P. Dell'Era, A. Gualandris, and M. Presta alpha vbeta 3 Integrin Mediates the Cell-adhesive Capacity and Biological Activity of Basic Fibroblast Growth Factor (FGF-2) in Cultured Endothelial Cells Mol. Biol. Cell, December 1, 1997; 8(12): 2449 - 2461. [Abstract] [Full Text]

				K.-P. Yip and D. J. Marsh An Arg-Gly-Asp peptide stimulates constriction in rat afferent arteriole Am J Physiol Renal Physiol, November 1, 1997; 273(5): F768 - F776. [Abstract] [Full Text] [PDF]

				S. Z. Domanico, A. J. Pelletier, W. L. Havran, and V. Quaranta Integrin alpha 6Abeta 1 Induces CD81-dependent Cell Motility without Engaging the Extracellular Matrix Migration Substrate Mol. Biol. Cell, November 1, 1997; 8(11): 2253 - 2265. [Abstract] [Full Text]

				A. J. Pelletier, T. Kunicki, and V. Quaranta Activation of the Integrin alpha(v)beta(3) Involves a Discrete Cation-binding Site That Regulates Conformation J. Biol. Chem., January 19, 1996; 271(3): 1364 - 1370. [Abstract] [Full Text] [PDF]

				H. S. Earp, W. R. Huckle, T. L. Dawson, X. Li, L. M. Graves, and R. Dy Angiotensin II Activates at Least Two Tyrosine Kinases in Rat Liver Epithelial Cells J. Biol. Chem., November 24, 1995; 270(47): 28440 - 28447. [Abstract] [Full Text] [PDF]

				X. Du, T. C. Saido, S. Tsubuki, F. E. Indig, M. J. Williams, and M. H. Ginsberg Calpain Cleavage of the Cytoplasmic Domain of the Integrin beta(3) Subunit J. Biol. Chem., November 3, 1995; 270(44): 26146 - 26151. [Abstract] [Full Text] [PDF]

				A. J. Pelletier, T. Kunicki, Z. M. Ruggeri, and V. Quaranta The Activation State of the Integrin [IMAGE][IMAGE][IMAGE][IMAGE] Affects Outside-in Signals Leading to Cell Spreading and Focal Adhesion Kinase Phosphorylation J. Biol. Chem., July 28, 1995; 270(30): 18133 - 18140. [Abstract] [Full Text] [PDF]

				S. Bhattacharya, C. Fu, J. Bhattacharya, and S. Greenberg Soluble Ligands of the [IMAGE][IMAGE][IMAGE][IMAGE] Integrin Mediate Enhanced Tyrosine Phosphorylation of Multiple Proteins in Adherent Bovine Pulmonary Artery Endothelial Cells J. Biol. Chem., July 14, 1995; 270(28): 16781 - 16787. [Abstract] [Full Text] [PDF]

				E. Clark and J. Brugge Integrins and signal transduction pathways: the road taken Science, April 14, 1995; 268(5208): 233 - 239. [Abstract] [PDF]

				M. J. Seckl, N. Morii, S. Narumiya, and E. Rozengurt Guanosine 5`-3-O-(Thio)triphosphate Stimulates Tyrosine Phosphorylation of p125[IMAGE] and Paxillin in Permeabilized Swiss 3T3 Cells J. Biol. Chem., March 24, 1995; 270(12): 6984 - 6990. [Abstract] [Full Text] [PDF]

				M Chrzanowska-Wodnicka and K Burridge Tyrosine phosphorylation is involved in reorganization of the actin cytoskeleton in response to serum or LPA stimulation J. Cell Sci., January 12, 1994; 107(12): 3643 - 3654. [Abstract] [PDF]

				W. S. Nesbitt, S. Kulkarni, S. Giuliano, I. Goncalves, S. M. Dopheide, C. L. Yap, I. S. Harper, H. H. Salem, and S. P. Jackson Distinct Glycoprotein Ib/V/IX and Integrin alpha IIbbeta 3-dependent Calcium Signals Cooperatively Regulate Platelet Adhesion under Flow J. Biol. Chem., January 18, 2002; 277(4): 2965 - 2972. [Abstract] [Full Text] [PDF]