The involvement of Gab1 and PI 3-kinase in beta1 integrin signaling in keratinocytes.
The control of the stem cell compartment in epidermis is closely linked to the regulation of keratinocyte proliferation and differentiation. Beta1 integrins are expressed 2-fold higher by stem cells than transit-amplifying cells. Signaling from these beta1 integrins is critical for the regulation of the epidermal stem cell compartment. To clarify the functional relevance of this differential expression of beta1 integrins, we established HaCaT cells with high beta1 integrin expression by repeated flow cytometric sorting of this population from the parental cell line. In these obtained cells expressing beta1 integrins by 5-fold, MAPK activation was markedly increased. Regarding the upstream of MAPK, Gab1 phosphorylation was also higher with high beta1 integrin expression, while Shc 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 beta1 integrin-mediated regulation of the epidermal stem cell compartment.
Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Yoshihiro
Y
Kuwano
Manabu
M
Fujimoto
Rei
R
Watanabe
Nobuko
N
Ishiura
Hiroko
H
Nakashima
Mayumi
M
Komine
Tatsuo S
TS
Hamazaki
Kunihiko
K
Tamaki
Hitoshi
H
Okochi
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D015603:Keratinocytes / Q000201:enzymology / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors
D048868:Adaptor Proteins, Signal Transducing; D048049:Extracellular Signal-Regulated MAP Kinases; D019012:Integrin beta1; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; C098587:GAB1 protein, human