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Gab1 and Mapk signaling are essential in the hair cycle and hair follicle stem cell quiescence

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Item Type:Article
Title:Gab1 and Mapk signaling are essential in the hair cycle and hair follicle stem cell quiescence
Creators Name:Akilli Öztürk, Ö. and Pakula, H. and Chmielowiec, J. and Qi, J. and Stein, S. and Lan, L. and Sasaki, Y. and Rajewsky, K. and Birchmeier, W.
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.
Keywords:Adult Stem Cells, Cell Self Renewal, Cultured Cells, GRB2 Adaptor Protein, Hair Follicle, Keratinocytes, MAP Kinase Kinase 1, MAP Kinase Signaling System, Non-Receptor Type 11 Protein Tyrosine Phosphatase, Phosphoproteins, Protein Binding, Animals, Mice
Source:Cell Reports
ISSN:2211-1247
Publisher:Cell Press / Elsevier (U.S.A.)
Volume:13
Number:3
Page Range:561-572
Date:20 October 2015
Official Publication:https://doi.org/10.1016/j.celrep.2015.09.015
PubMed:View item in PubMed

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