title: Participation of Gab1 and Gab2 in IL-22-mediated keratinocyte proliferation, migration, and differentiation.
abstract: Interleukin-22 (IL-22) is one of the key mediators of keratinocyte alterations in psoriasis. IL-22 inhibits keratinocyte differentiation and induces the migration of human keratinocytes. Grb2-associated binder 1 (Gab1) has been shown to mediate epidermal growth factor-induced epidermal growth and differentiation via interaction with the Src homology-2-containing protein-tyrosine phosphatase (Shp2). In this investigation, we explore the role of Gab1 and Gab2 in IL-22-mediated keratinocyte activities. We show that both Gab1 and Gab2 were tyrosine phosphorylated in IL-22-stimulated HaCaT cells and human primary epidermal keratinocytes and contributed to the activation of Extracellular signal regulated kinase 1/2 (Erk1/2) through interaction with Shp2. We further demonstrate that HaCaT cells infected with adenoviruses expressing Shp2-binding-defective Gab1/2 mutants exhibited decreased cell proliferation and migration, as well as increased differentiation. Moreover, similar results were observed in HaCaT cells infected with adenovirus-based small interfering RNAs targeting Gab1 and/or Gab2. Altogether, these data underscore the critical roles of Gab1 and Gab2 in IL-22-mediated HaCaT cell proliferation, migration, and differentiation.
authors.affiliation: Department of Dermatology of Clinical Medical School, Yangzhou University, Yangzhou, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Zhu
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Li
authors.forename: Wenyan
authors.initials: W
authors.lastname: Pan
authors.forename: Lu
authors.initials: L
authors.lastname: Qin
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Zhu
authors.forename: Yuehai
authors.initials: Y
authors.lastname: Ke
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Ping
authors.initials: P
authors.lastname: Bo
authors.forename: Songshu
authors.initials: S
authors.lastname: Meng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D011565:Psoriasis / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007378:Interleukins; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D014443:Tyrosine; D000097043:Interleukin-22; C098587:GAB1 protein, human; C490895:GAB2 protein, human; C516724:PTPN11 protein, human