Structure and function of Gab2 and its role in cancer (Review)
Open accessAbstract
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.
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Many cell signaling pathways require large multi-site docking proteins to transduce signal from the activated receptor to downstream intracellular effectors.
“Many cell signaling pathways require large multi-site docking proteins to transduce signal from the activated receptor to downstream intracellular effectors [305].”
From Intrinsically disordered proteins play diverse roles in cell signaling (2022) · cites this paper as [305]
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- Authors
- DING, C.-B., YU, W.-N., FENG, J.-H., & LUO, J.-M.
- Venue
- Molecular Medicine Reports
- Publisher
- Spandidos Publications
- Published
- 2015-06-17
- Volume
- 12
- Issue
- 3
- Pages
- 4007-4014
- ISSN
- 1791-2997 (ISSN-L)
- 1791-3004
- PMC
- PMC4526075
- OpenAlex
- W2145250151
- Cited by
- 71
- References
- 84
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 8 · 2023: 5 · 2022: 18 · 2021: 8 · 2020: 4 · 2019: 7 · 2018: 3 · 2017: 6 · 2016: 6
- FWCI
- 0.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Molecular Medicine Reports (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Guizhou Science and Technology Department (2013J2312)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- Gab2, docking protein, signal transduction, SH2 domain proteins, SHP2, phosphatidylinositol 3-kinase, PLCγ1, Crk, MAPK signaling, PI3K/Akt signaling, protein-protein interaction, carcinogenesis, breast cancer, leukemia, melanoma, therapeutic target
- MeSH terms
- Humans, Neoplasms, Signal Transduction, Phosphatidylinositol 3-Kinases, Mitogen-Activated Protein Kinase Kinases, Adaptor Proteins, Signal Transducing, Phospholipase C gamma, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Interaction Domains and Motifs
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