SEARCH:   Advanced

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yu, W.-M. Articles by Qu, C.-K. Search for Related Content PubMed PubMed Citation Articles by Yu, W.-M. Articles by Qu, C.-K. Related Collections Hematopoiesis and Stem Cells Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 April 2002, Vol. 99, No. 7, pp. 2351-2359 HEMATOPOIESIS Role of the docking protein Gab2 in 1-integrin signaling pathway-mediated hematopoietic cell adhesion and migration Wen-Mei Yu, Teresa S. Hawley, Robert G. Hawley, and Cheng-Kui Qu From the Department of Hematopoiesis, Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, MD, and Department of Anatomy and Cell Biology, George Washington University School of Medicine and Health Sciences, Washington, DC. Gab2, a newly identified pleckstrin homology domain-containing docking protein, is a major binding protein of SHP-2 tyrosine phosphatase in interleukin (IL)-3-stimulated hematopoietic cells. Its signaling mechanism remains largely unknown. We report here an important regulatory role for Gab2 in 1 integrin signaling pathway that mediates hematopoietic cell adhesion and migration. Cross-linking of the 1 integrin on Ba/F3 cells induced rapid tyrosine phosphorylation of Gab2 and its association with Syk kinase, SHP-2 phosphatase, and the p85 subunit of phosphatidylinositol (PI)-3 kinase. In addition, Gab2 was also constitutively associated with SHP-1 phosphatase via its C-terminal Src homology 2 domain. Overexpression of the pleckstrin homology domain or a mutant Gab2 molecule lacking SHP-2 binding sites resulted in significant reductions in Ba/F3 cell adhesion and migration. Biochemical analyses revealed that enforced expression of Gab2 mutant molecules dramatically reduced 1-integrin ligation-triggered PI3 kinase activation, whereas Erk kinase activation remained unaltered. Furthermore, transduction of primary hematopoietic progenitor cells from viable motheaten mice with these mutant Gab2 molecules also significantly ameliorated their enhanced migration capacity associated with the SHP1 gene mutation. Taken together, these results suggest an important signaling role for Gab2 in regulating hematopoietic cell adhesion and migration. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Wang, W.-M. Yu, W. Zhang, K. R. McCrae, B. G. Neel, and C.-K. Qu Noonan Syndrome/Leukemia-associated Gain-of-function Mutations in SHP-2 Phosphatase (PTPN11) Enhance Cell Migration and Angiogenesis J. Biol. Chem., January 9, 2009; 284(2): 913 - 920. [Abstract] [Full Text] [PDF] Y. Zhang, E. Diaz-Flores, G. Li, Z. Wang, Z. Kang, E. Haviernikova, S. Rowe, C.-K. Qu, W. Tse, K. M. Shannon, et al. Abnormal hematopoiesis in Gab2 mutant mice Blood, July 1, 2007; 110(1): 116 - 124. [Abstract] [Full Text] [PDF] M. Yu, J. Luo, W. Yang, Y. Wang, M. Mizuki, Y. Kanakura, P. Besmer, B. G. Neel, and H. Gu The Scaffolding Adapter Gab2, via Shp-2, Regulates Kit-evoked Mast Cell Proliferation by Activating the Rac/JNK Pathway J. Biol. Chem., September 29, 2006; 281(39): 28615 - 28626. [Abstract] [Full Text] [PDF] J. H. Lee, Y. M. Kim, N. W. Kim, J. W. Kim, E. Her, B. K. Kim, J. H. Kim, S. H. Ryu, J. W. Park, D. W. Seo, et al. Phospholipase D2 acts as an essential adaptor protein in the activation of Syk in antigen-stimulated mast cells Blood, August 1, 2006; 108(3): 956 - 964. [Abstract] [Full Text] [PDF] D. Imhof, A.-S. Wavreille, A. May, M. Zacharias, S. Tridandapani, and D. Pei Sequence Specificity of SHP-1 and SHP-2 Src Homology 2 Domains: CRITICAL ROLES OF RESIDUES BEYOND THE pY+3 POSITION J. Biol. Chem., July 21, 2006; 281(29): 20271 - 20282. [Abstract] [Full Text] [PDF] M. Yu, C. A. Lowell, B. G. Neel, and H. Gu Scaffolding Adapter Grb2-Associated Binder 2 Requires Syk to Transmit Signals from Fc{epsilon}RI J. Immunol., February 15, 2006; 176(4): 2421 - 2429. [Abstract] [Full Text] [PDF] T. Brummer, D. Schramek, V. M. Hayes, H. L. Bennett, C. E. Caldon, E. A. Musgrove, and R. J. Daly Increased Proliferation and Altered Growth Factor Dependence of Human Mammary Epithelial Cells Overexpressing the Gab2 Docking Protein J. Biol. Chem., January 6, 2006; 281(1): 626 - 637. [Abstract] [Full Text] [PDF] R. V. Parry, G. C. Whittaker, M. Sims, C. E. Edmead, M. J. Welham, and S. G. Ward Ligation of CD28 Stimulates the Formation of a Multimeric Signaling Complex Involving Grb-2-Associated Binder 2 (Gab2), Src Homology Phosphatase-2, and Phosphatidylinositol 3-Kinase: Evidence That Negative Regulation of CD28 Signaling Requires the Gab2 Pleckstrin Homology Domain J. Immunol., January 1, 2006; 176(1): 594 - 602. [Abstract] [Full Text] [PDF] Y. Mao and A. W.-M. Lee A novel role for Gab2 in bFGF-mediated cell survival during retinoic acid-induced neuronal differentiation J. Cell Biol., July 18, 2005; 170(2): 305 - 316. [Abstract] [Full Text] [PDF] S. Kraft, T. Fleming, J. M. Billingsley, S.-Y. Lin, M.-H. Jouvin, P. Storz, and J.-P. Kinet Anti-CD63 antibodies suppress IgE-dependent allergic reactions in vitro and in vivo J. Exp. Med., February 7, 2005; 201(3): 385 - 396. [Abstract] [Full Text] [PDF] K. D. Moon, C. B. Post, D. L. Durden, Q. Zhou, P. De, M. L. Harrison, and R. L. Geahlen Molecular Basis for a Direct Interaction between the Syk Protein-tyrosine Kinase and Phosphoinositide 3-Kinase J. Biol. Chem., January 14, 2005; 280(2): 1543 - 1551. [Abstract] [Full Text] [PDF] M. Arnaud, C. Crouin, C. Deon, D. Loyaux, and J. Bertoglio Phosphorylation of Grb2-Associated Binder 2 on Serine 623 by ERK MAPK Regulates Its Association with the Phosphatase SHP-2 and Decreases STAT5 Activation J. Immunol., September 15, 2004; 173(6): 3962 - 3971. [Abstract] [Full Text] [PDF] Q.-S. Zhu, L. J. Robinson, V. Roginskaya, and S. J. Corey G-CSF-induced tyrosine phosphorylation of Gab2 is Lyn kinase dependent and associated with enhanced Akt and differentiative, not proliferative, responses Blood, May 1, 2004; 103(9): 3305 - 3312. [Abstract] [Full Text] [PDF] W.-M. Yu, T. S. Hawley, R. G. Hawley, and C.-K. Qu Immortalization of yolk sac-derived precursor cells Blood, November 15, 2002; 100(10): 3828 - 3831. [Abstract] [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020