The alpha 5 beta 1 integrin supports survival of cells on fibronectin and up-regulates Bcl-2 expression.
Anchorage-dependent cells that are prevented from attaching to an extracellular matrix substrate stop proliferating and may undergo apoptosis. Cell adhesion to a substrate is mediated by the integrin family of cell surface receptors, which are known to elicit intracellular signals upon cell adhesion. We show here that Chinese hamster ovary cells expressing the alpha 5 beta 1 integrin, which is a fibronectin receptor, do not undergo apoptosis upon serum withdrawal when the cells are plated on fibronectin. However, the alpha v beta 1 integrin, which is also a fibronectin receptor and binds fibronectin on the same RGD motif as alpha 5 beta 1, did not prevent apoptosis on fibronectin of the same cells. The cytoplasmic domain of the integrin alpha 5 subunit was required for the alpha 5 beta 1-mediated cell survival on fibronectin. The fibronectin-mediated survival effect appeared to be independent of the level of tyrosine phosphorylation of the focal adhesion kinase, which is induced by integrin-mediated cell attachment. The expression of the Bcl-2 protein, which counteracts apoptosis, was elevated in cells attaching to fibronectin through alpha 5 beta 1; cells attaching through alpha v beta 1 survived only if exogenous Bcl-2 was provided. Thus, alpha 5 beta 1, but not the closely related alpha v beta 1 integrin, appears to suppress apoptotic cell death through the Bcl-2 pathway.
Zhang
Z
Z
Cancer Research Center, La Jolla Cancer Research Foundation, CA 92037, USA.
Vuori
K
K
Reed
J C
JC
Ruoslahti
E
E
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D016466:CHO Cells; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D006224:Cricetinae; D004247:DNA / Q000032:analysis; D017931:DNA Primers; D005353:Fibronectins; D005786:Gene Expression Regulation; D016023:Integrins / Q000096:biosynthesis / Q000502:physiology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes; D017469:Receptors, Fibronectin / Q000502:physiology*; D019030:Receptors, Vitronectin; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection
D017931:DNA Primers; D005353:Fibronectins; D016023:Integrins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017469:Receptors, Fibronectin; D019030:Receptors, Vitronectin; D011994:Recombinant Proteins; C094340:integrin alphavbeta1; D004247:DNA; D011505:Protein-Tyrosine Kinases