The beta 4 integrin subunit rescues A431 cells from apoptosis through a PI3K/Akt kinase signaling pathway

To study whether alpha 6 beta 4 integrin regulates apoptosis, human A431 ce lls were plated on bacteria plates in the presence or absence of mAb beta 4 . In the absence of mAb beta 4, A431 cells demonstrated morphological chara cteristics of apoptosis by 24 h and most cells died by 48 h. In contrast, i n the presence of mAb beta 4, cells remained viable, and at the end of 48 h , 70-80% of cells survived. Treatment of A431 cells with mAb beta 4 resulte d in tyrosine phosphorylation of the p85 subunit of PI3 kinase; PI3 kinase activity increased within 15 min and peaked at 60 min, Stimulation of beta 4 in A431 cells resulted in a time-dependent phosphorylation of Akt with a concomitant and parallel phosphorylation of Bad. Inactivation of PI3 kinase with inhibitors blocked the anti-apoptotic effect induced by mAb beta 4, T hese are the first results to suggest that ligation of beta 6 beta 4 integr in protects cells from apoptosis through a PI3K/Akt kinase signaling pathwa y. (C) 1999 Academic Press.