title: Structure and function of Gab2 and its role in cancer (Review).
abstract: The docking proteins of the Grb-associated binder (Gab) family transduce cellular signals between receptors and intracellular downstream effectors, and provide a platform for protein‑protein interactions. Gab2, a key member of the Gab family of proteins, is involved in the amplification and integration of signal transduction, evoked by a variety of extracellular stimuli, including growth factors, cytokines and antigen receptors. Gab2 protein lacks intrinsic catalytic activity; however, when phosphorylated by protein‑tyrosine kinases (PTKs), Gab2 recruits several Src homology‑2 (SH2) domain‑containing proteins, including the SH2‑containing protein tyrosine phosphatase 2 (SHP2), the p85 subunit of phosphoinositide‑3 kinase (PI3K), phospholipase C‑γ (PLCγ)1, Crk, and GC‑GAP. Through these interactions, the Gab2 protein triggers various downstream signal effectors, including SHP2/rat sarcoma viral oncogene/RAF/mitogen‑activated protein kinase kinase/extracellular signal‑regulated kinase and PI3K/AKT, involved in cell growth, differentiation, migration and apoptosis. It has been previously reported that aberrant Gab2 and/or Gab2 signaling is closely associated with human tumorigenesis, particularly in breast cancer, leukemia and melanoma. The present review aimed to focus on the structure and effector function of Gab2, its role in cancer and its potential for use as an effective therapeutic target.
authors.affiliation: Department of Immunology and Immunology Innovation Base for Postgraduate Education in Guizhou Province, Zunyi Medical University, Zunyi, Guizhou 563099, P.R. China.
authors.forename: Chen-Bo
authors.initials: CB
authors.lastname: Ding
authors.affiliation: Department of Immunology and Immunology Innovation Base for Postgraduate Education in Guizhou Province, Zunyi Medical University, Zunyi, Guizhou 563099, P.R. China.
authors.forename: Wei-Na
authors.initials: WN
authors.lastname: Yu
authors.affiliation: Department of Oncology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563099, P.R. China.
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Feng
authors.affiliation: Department of Immunology and Immunology Innovation Base for Postgraduate Education in Guizhou Province, Zunyi Medical University, Zunyi, Guizhou 563099, P.R. China.
authors.forename: Jun-Min
authors.initials: JM
authors.lastname: Luo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C490895:GAB2 protein, human; D019869:Phosphatidylinositol 3-Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D051966:Phospholipase C gamma