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Vol. 11, Issue 6, 1973-1987, June 2000
5
1 Integrin Protects Intestinal Epithelial Cells
from Apoptosis through a Phosphatidylinositol 3-Kinase and
Protein Kinase B-dependent Pathway
Department of Pharmacology, School of Medicine, University of North
Carolina, Chapel Hill, North Carolina 27599-7365
Renewal of the gastrointestinal epithelium involves a coordinated
process of terminal differentiation and programmed cell death.
Integrins have been implicated in the control of apoptotic processes in various cell types. Here we examine the role of
integrins in the regulation of apoptosis in gastrointestinal
epithelial cells with the use of a rat small intestinal epithelial cell
line (RIE1) as a model. Overexpression of the integrin 
5
subunit in RIE1 cells conferred protection against several proapoptotic
stimuli. In contrast, overexpression of the integrin 2
subunit had no effect on cell survival. The antiapoptotic effect of the
5 subunit was partially retained by a mutated version that had a
truncation of the cytoplasmic domain. The antiapoptotic effects of the
full-length or truncated 5 subunit were reversed upon treatment with
inhibitors of phosphatidylinositol 3-kinase (PI-3-kinase),
suggesting that the 5
1 integrin might interact with the
PI-3-kinase/Akt survival pathway. When cells overexpressing 5 were
allowed to adhere to fibronectin, there was a moderate activation of
protein kinase B (PKB)/Akt, whereas no such effect was seen in
2-overexpressing cells adhering to collagen. Furthermore, in cells
overexpressing 5 and adhering to fibronectin, there was a dramatic
enhancement of the ability of growth factors to stimulate PKB/Akt;
again, this was not seen in cells overexpressing 2 subunit and
adhering to collagen or fibronectin. Expression of a dominant negative version of PKB/Akt in RIE cells blocked to ability of 5 to enhance cell survival. Thus, the 51 integrin seems to protect
intestinal epithelial cells against proapoptotic stimuli by selectively
enhancing the activity of the PI-3-kinase/Akt survival pathway.
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