The alpha5beta1 integrin selectively enhances epidermal growth factor signaling to the phosphatidylinositol-3-kinase/Akt pathway in intestinal epithelial cells.
We have investigated EGF-driven signaling processes in rat intestinal epithelial cell lines that overexpress either the alpha5beta1 integrin or the alpha2beta1 integrin. Both cell types display efficient activation of Erk/MAP kinase, but only the alpha5beta1 expressing cells display a strong activation of Akt. A complex is formed between activated EGFR and alpha5beta1, but not with alpha2beta1; this complex also contains ErbB3 and p85. Thus alpha5beta1 can support efficient activation of both the Erk and the phosphatidylinositol-3-kinase/Akt branches of the EGFR signaling cascade, whereas alpha2beta1 can support only the Erk branch.
Lee
Jung Weon
JW
Department of Pharmacology, School of Medicine, University of North Carolina, 1106 Mary Ellen Jones Building, Chapel Hill, NC 27599-7365, USA.
Juliano
R L
RL
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells / Q000378:metabolism; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism; D051380:GRB2 Adaptor Protein; D016023:Integrins / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D038981:Receptors, Collagen; D017469:Receptors, Fibronectin / Q000096:biosynthesis* / Q000737:chemistry; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D051380:GRB2 Adaptor Protein; D016023:Integrins; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D038981:Receptors, Collagen; D017469:Receptors, Fibronectin; C495950:Grb2 protein, rat; C494920:Akt1 protein, rat