Aj. Zhu et al., Signaling via beta 1 integrins and mitogen-activated protein kinase determines human epidermal stem cell fate in vitro, P NAS US, 96(12), 1999, pp. 6728-6733
Citations number
34
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Human epidermal stem cells express higher levels of beta 1 integrins and ar
e more adhesive than keratinocytes that are destined to differentiate. To i
nvestigate whether high beta 1 integrin expression and adhesiveness are ess
ential for maintaining keratinocytes in the stem cell compartment, we intro
duced a dominant-negative beta 1 integrin mutant, CD8 beta 1, into cultured
human keratinocytes, thereby interfering with beta 1 integrin function. Su
rface beta 1 integrin levels, adhesiveness, and mitogen-activated protein (
MAP) kinase activation on fibronectin were reduced, and exit from the stem
cell compartment was stimulated. Adhesiveness and proliferative potential w
ere restored by overexpressing wild-type beta 1 integrin or by constitutive
MAP kinase activation. Conversely, a dominant-negative MAP kinase kinase 1
mutant decreased adhesiveness and stem cell number in the absence of CD8 b
eta 1, MAP kinase activation by alpha 6 beta 4-mediated adhesion and mitoge
ns was normal in CD8 beta 1 cells, and constitutive MAP kinase activation d
id not affect adhesion and proliferation of control keratinocytes, We concl
ude that beta 1 integrins and MAP kinase cooperate to maintain the epiderma
l stem cell compartment in vitro.