Because inhibition of integrin signaling induces apoptosis, we investigated whether keratinocytes expressing L1 and K6L4 integrins (enriched for stem cells)are protected from cell death. Keratinocytes rapidly adhering to type IV collagen expressed highest levels of L1 and K6L4 and of the anti-apoptotic stem cell marker p63. Apoptotic cells were signi¢cantly higher in slowly adhering than in rapidly adhering keratinocytes. AntiL1 integrin caused a signi¢cant increase in apoptotic cells, while it decreased Bcl-2 levels in stem keratinocytes. Bax and Bad proteins were higher in slowly adhering than in rapidly adhering cells. By contrast, Bcl-2, Bcl-x and Mcl-1 proteins were highest in rapidly adhering keratinocytes and nearly absent in slowly adhering cells. After addition of anti-L1 integrin, the apoptotic rate was signi¢cantly higher in HaCaT cells not expressing Bcl-2 than in controls. These results indicate that keratinocytes enriched for stem cells are protected from apoptosis via L1 integrin, in a Bcl-2 dependent manner. , 2002 Federation of European Biochemical Societies.