The control of the stem cell compartment in epidermis is closely linked to the regulation of keratinocyte proliferation and differentiation. beta 1 integrins are expressed 2-fold higher by stem cells than transit-amplifying cells. Signaling from these beta 1 integrins is critical for the regulation of the epidermal stem cell compartment. To clarify the functional relevance of this differential expression of beta 1 integrins, we established HaCaT cells with high beta 1integrin expression by repeated flow cytometric sorting of this population from the parental cell line. In these obtained cells expressing beta 1 integrins by 5-fold, MAPK activation was markedly increased. Regarding the upstream of MAPK, Gab I phosphorylation was also higher with high beta 1 integrin expression, while She phosphorylation was not altered. In addition, enhanced phosphatidylinositol 3-kinase activation was also observed. These observations suggest that Gab1 and phosphatidylinositol 3-kinase play pivotal roles in the beta 1 integrin-mediated regulation of the epidermal stem cell compartment. (C) 2007 Elsevier Inc. All rights reserved.