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.

Dorsal Ruffles Enhance Activation of Akt by Growth Factors

“…Such barriers should confine phospholipids or the enzymes that modify them within CDR and cups, consequently localizing signal cascades to these regions of plasma membrane (Welliver and Swanson, 2012). PIP3 synthesized by PI3K within CDR may be retained there by the diffusion barrier, allowing positive feedback stimulation of PI3K by PIP3, which could be mediated by Ras, Rac or the adapter protein Gab1 (Rodrigues et al, 2000, Castellano and Downward, 2011, Fritsch et al, 2013, Ding et al, 2015. The elevated concentrations PIP3 within CDR could also enhance barrier formation through activation of Rac1 or Ras (Kay et al, 2018, Delos Santos et al, 2015, Hoon et al, 2012, Lien et al, 2017.…”

Dorsal ruffles enhance activation of Akt by growth factors

“…Such barriers should confine phospholipids or the enzymes that modify them within CDRs and cups, consequently localizing signal cascades to these regions of plasma membrane (Welliver and Swanson, 2012). PIP 3 synthesized by PI3K within CDRs might be retained there by the diffusion barrier, allowing positive feedback stimulation of PI3K by PIP 3 , which could be mediated by Ras, Rac or the adapter protein Gab1 (Rodrigues et al, 2000;Castellano and Downward, 2011;Fritsch et al, 2013;Ding et al, 2015). The elevated concentrations of PIP 3 within CDRs could also enhance barrier formation through activation of Rac1 or Ras (Kay et al, 2018;Delos Santos et al, 2015;Hoon et al, 2012;Lien et al, 2017).…”

Lipid quantification by Raman microspectroscopy as a potential biomarker in prostate cancer

“…Specifically, the active forms of MAPK and ERBB2 are reported to be involved with cell cycle regulation and involved in metastasis and resistance to androgen deprivation therapy, respectively [50–52]. Whereas, GAB2 is a known regulator of PI3K and STAT5A is critical for PCa cell survival and growth, and overexpression of both proteins coincides with FASN expression [53, 54]. Interestingly, DIABLO and DDP4 were under-expressed with FASN expression.…”