title: Requirement of Gαi1/3-Gab1 signaling complex for keratinocyte growth factor-induced PI3K-AKT-mTORC1 activation.
abstract: Keratinocyte growth factor (KGF), also termed as fibroblast growth factor-7, promotes proliferation, migration, and adhesion of skin keratinocytes via binding to keratinocyte growth factor receptor (KGFR) and subsequent activation of downstream signaling including the PI3K-AKT-mTORC1 pathway. Here, we found that the α-subunits of the G proteins (Gαi1/3) and growth factor receptor binding 2-associated binding protein 1 (Gab1) are required for this activation process. With KGF stimulation, Gαi1/3 formed a complex with KGFR and was required for subsequent Gab1 recruitment, phosphorylation, and following PI3K-p85 activation. In addition, Gαi1/3 short hairpin RNA knockdown largely inhibited KGF-induced cell proliferation, migration, and the accumulation of cyclin D1/fibronectin in cultured skin keratinocytes. Furthermore, we observed increased expression of Gαi1/3 in wounded human skin and keloid skin tissues, suggesting the possible involvement of Gαi1/3 in wound healing and keloid formation. Overall, we suggest that Gαi1/3 proteins lie downstream of KGFR, but upstream of Gab1-mediated activation of PI3K-AKT-mTORC1 signaling, thus revealing a role for Gαi proteins in mediating KGFR signaling, cell migration, and possible wound healing.
authors: Department of Plastic and Cosmetic Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors: Yi-Ming
authors: YM
authors: Zhang
authors: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, Soochow University, Suzhou, China.
authors: Zhi-Qing
authors: ZQ
authors: Zhang
authors: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, Soochow University, Suzhou, China.
authors: Yuan-Yuan
authors: YY
authors: Liu
authors: Department of Plastic and Cosmetic Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors: Xin
authors: X
authors: Zhou
authors: Department of Plastic and Cosmetic Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors: Xiao-Hua
authors: XH
authors: Shi
authors: The Affiliated Eye Hospital, Nanjing Medical University, Nanjing City, China. Electronic address: Jqin710@vip.sina.com.
authors: Qin
authors: Q
authors: Jiang
authors: Department of Plastic and Cosmetic Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China. Electronic address: fdltmmu@sina.com.
authors: Dong-Li
authors: DL
authors: Fan
authors: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, Soochow University, Suzhou, China. Electronic address: caocong@suda.edu.cn.
authors: Cong
authors: C
authors: Cao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D051523:Fibroblast Growth Factor 7 / Q000378:metabolism; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000235:genetics / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D007627:Keloid / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D012867:Skin / Q000166:cytology / Q000293:injuries / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051523:Fibroblast Growth Factor 7; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D058570:TOR Serine-Threonine Kinases; C496453:FGF7 protein, human; C098587:GAB1 protein, human; C584114:GNAI1 protein, human; C498015:GNAI2 protein, human; C498819:GNAI3 protein, human