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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 2001, Vol. 97, No. 7, pp. 1975-1981 HEMATOPOIESIS Cross-talk between 41/51 and c-Kit results in opposing effect on growth and survival of hematopoietic cells via the activation of focal adhesion kinase, mitogen-activated protein kinase, and Akt signaling pathways Reuben Kapur, Ryan Cooper, Lei Zhang, and David A. Williams From The Section of Pediatric Hematology/Oncology, Department of Pediatrics, Herman B Wells Center for Pediatric Research, James Whitcomb Riley Hospital for Children, The Howard Hughes Medical Institute, Indiana University School of Medicine, Indianapolis, Indiana. Erythroid progenitor cells (EPCs) are deficient in mice lacking either the ligand stem cell factor (SCF), its receptor c-Kit, or 1-integrins. In nonhematopoietic cells, integrins and receptor tyrosine kinases can collaborate to modulate cellular functions, providing evidence for cross-talk between signals emerging from these cell surface molecules. Using specific recombinant fibronectin peptides that contain the binding site for the integrin 41 (FN-H296) or 51 (FN-CH271) or both 41 and 51 (FN-CH296), this study investigated the effect of adhesion alone, or in combination with activation of c-Kit, on functional and biochemical outcomes in an EPC line, G1E-ER2, and primary EPCs. G1E-ER2 cells and primary EPCs cultured on FN-CH271 in the presence of c-Kit activation led to a significant increase in proliferation in comparison with cells grown on FN-H296 or FN-CH296. G1E-ER2 cells cultured on FN-H296 or FN-CH296 resulted in significant cell death in comparison to cells grown on FN-CH271. Activation of c-Kit enhanced the survival of G1E-ER2 cells grown on FN-H296 or FN-CH296; however, the rescue was only partial. The reduced survival of G1E-ER2 cells on FN-H296 correlated with reduced activation of Akt and expression of Bcl-2 and Bcl-xL, whereas increase in proliferation on FN-CH271 correlated with significantly enhanced and sustained activation of focal adhesion kinase (FAK) and extracellular-regulated kinase (ERK) pathways. These data demonstrate that adhesion-induced signals emanating from ligation of 41 and 51 result in distinct biologic outcomes, including death via 41 and survival/proliferation via 51. © 2001 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: Y. Jiang, H. Bonig, T. Ulyanova, K. Chang, and T. Papayannopoulou On the adaptation of endosteal stem cell niche function in response to stress Blood, October 29, 2009; 114(18): 3773 - 3782. [Abstract] [Full Text] [PDF] R. Tanaka, T. Owaki, S. Kamiya, T. Matsunaga, K. Shimoda, H. Kodama, R. Hayashi, T. Abe, Y. P. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020