title: Gab1 and Mapk Signaling Are Essential in the Hair Cycle and Hair Follicle Stem Cell Quiescence.
abstract: Gab1 is a scaffold protein that acts downstream of receptor tyrosine kinases. Here, we produced conditional Gab1 mutant mice (by K14- and Krox20-cre) and show that Gab1 mediates crucial signals in the control of both the hair cycle and the self-renewal of hair follicle stem cells. Remarkably, mutant hair follicles do not enter catagen, the destructive phase of the hair cycle. Instead, hair follicle stem cells lose quiescence and become exhausted, and thus no stem cell niches are established in the bulges. Moreover, conditional sustained activation of Mapk signaling by expression of a gain-of-function Mek1(DD) allele (by Krox20-cre) rescues hair cycle deficits and restores quiescence of the stem cells. Our data thus demonstrate an essential role of Gab1 downstream of receptor tyrosine kinases and upstream of Shp2 and Mapk in the regulation of the hair cycle and the self-renewal of hair follicle stem cells.
authors.affiliation: Signaling in Development and Cancer, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin-Buch, Germany.
authors.forename: Özlem
authors.initials: Ö
authors.lastname: Akilli Öztürk
authors.affiliation: Signaling in Development and Cancer, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin-Buch, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Pakula
authors.affiliation: Signaling in Development and Cancer, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin-Buch, Germany.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Chmielowiec
authors.affiliation: Signaling in Development and Cancer, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin-Buch, Germany.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Qi
authors.affiliation: Signaling in Development and Cancer, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin-Buch, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Stein
authors.affiliation: Signaling in Development and Cancer, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin-Buch, Germany.
authors.forename: Linxiang
authors.initials: L
authors.lastname: Lan
authors.affiliation: Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Immune Regulation and Cancer, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin-Buch, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Rajewsky
authors.affiliation: Signaling in Development and Cancer, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin-Buch, Germany. Electronic address: wbirch@mdc-berlin.de.
authors.forename: Walter
authors.initials: W
authors.lastname: Birchmeier
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D000066673:Cell Self Renewal; D002478:Cells, Cultured; D051380:GRB2 Adaptor Protein / Q000378:metabolism; D018859:Hair Follicle / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D048369:MAP Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C490897:Gab1 protein, mouse; C495949:Grb2 protein, mouse; D010750:Phosphoproteins; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; C516725:Ptpn11 protein, mouse