| 2002 |
Gab3 contains an amino-terminal pleckstrin homology (PH) domain, multiple tyrosine phosphorylation sites, and polyproline motifs. After M-CSF receptor (Fms) stimulation, Gab3 is tyrosine phosphorylated and transiently associates with the SH2 domain-containing proteins p85 (PI3K regulatory subunit) and SHP2. Overexpression of Gab3 in FD-Fms cells dramatically accelerates macrophage differentiation upon M-CSF stimulation, and differentiation requires early phosphorylation of Gab2 followed by induction and phosphorylation of Gab3. |
Co-immunoprecipitation, overexpression in FDC-P1/FD-Fms cell lines, mRNA expression analysis, M-CSF stimulation assays, mutant receptor lines (Y807F, Y807F) |
Molecular and cellular biology |
Medium |
11739737
|
| 2002 |
Gab3 interacts specifically with the adapter protein Mona/Gads (but not with the related adapter Grb2 in the same context distinguishing it from Gab2) during monocyte/macrophage differentiation. GST pull-down experiments demonstrated that this interaction requires the carboxy-terminal SH3 domain of Mona and the atypical proline-rich domain of Gab3. Gab3 also forms a complex with the Mona-related adapter Grb2. The M-CSFR Y697F mutation reduced Gab3 tyrosine phosphorylation and Mona induction, while Y807F (differentiation-defective) also failed to induce Mona expression. |
GST pull-down, co-immunoprecipitation, mutant M-CSF receptor lines (Y697F, Y807F), immunoblotting during bone marrow macrophage differentiation |
Molecular and cellular biology |
High |
11997510
|
| 2003 |
Gab3-deficient (Gab3-/-) mice develop normally with intact hematopoiesis: macrophages develop in normal numbers and exhibit normal function; T- and B-lymphocyte responses to protein antigens, viral infection, and allergic responses are unimpaired. Loss of Gab3 is not compensated by increased Gab1 or Gab2 mRNA levels. |
Homologous recombination knockout, generation of Gab3-specific monoclonal antibodies, immunoblotting, flow cytometry, functional immune assays |
Molecular and cellular biology |
High |
12640125
|
| 2019 |
Gab3 is required for IL-2- and IL-15-induced NK cell priming and expansion. Loss of Gab3 selectively impairs MAPK signaling (ERK activation) downstream of cytokine receptors but does not affect STAT5 signaling. In vivo, Gab3-deficient mice show impaired elimination of 'missing-self' and tumor targets. Additionally, Gab3 is required for uterine NK cell expansion; its absence causes abnormal spiral artery remodeling, increased trophoblast invasion, and pregnancy complications. |
Gab3-/- mouse model, cytokine stimulation assays, MAPK and STAT5 phosphorylation analysis (signaling pathway dissection), in vivo tumor challenge, NK cell functional assays, histological analysis of placenta |
Science immunology |
High |
31375526
|
| 2019 |
Gab2 and Gab3 redundantly suppress colitis by modulating macrophage and CD8+ T-cell activation. Gab2/3 double knockout (but not single knockouts) develop spontaneous colitis. Reciprocal bone marrow transplantation established that the disease-initiating process is hematopoietic cell-intrinsic. Mechanistically, loss of Gab2/3 reduces PI3-kinase/Akt/mTORC1 signaling in macrophages and T-cells, while IL-2-stimulated T-cells show increased pSTAT5. |
Double-knockout mouse generation, reciprocal bone marrow transplantation, adoptive transfer, PI3K/Akt/mTORC1 and STAT5 phosphorylation analysis |
Frontiers in immunology |
Medium |
30936879
|
| 2017 |
In colorectal cancer cells, Gab3 co-precipitates with p85 (PI3K regulatory subunit) and SHP2, and this association is required for subsequent Akt and Erk activation. Gab3 knockdown inhibits Akt and Erk activation, while Gab3 overexpression augments it, promoting CRC cell proliferation. |
Co-immunoprecipitation, shRNA/siRNA knockdown, overexpression, Akt and Erk phosphorylation analysis, xenograft tumor model |
Biochemical and biophysical research communications |
Medium |
28115166
|
| 2017 |
In glioma cells, Gab3 knockdown (shRNA/siRNA) significantly inhibits Akt activation and cell proliferation, while forced Gab3 overexpression promotes Akt activation and cell proliferation. In vivo xenograft tumor growth is inhibited by Gab3 shRNA with corresponding suppression of Akt activation. |
shRNA/siRNA knockdown, overexpression, Akt phosphorylation analysis, xenograft tumor model in nude mice |
PloS one |
Medium |
28291820
|
| 2024 |
GAB3 interacts with RSK kinases (p90 ribosomal S6 kinases) through a DDVF-like short linear motif (SLiM), using the same docking interface exploited by viral and bacterial pathogen proteins. Co-immunoprecipitation confirmed that GAB3 is a novel RSK-binding partner. GAB3 and other DDVF-like SLiM-containing proteins act upstream of RSK in the RAS-ERK MAPK pathway, and RSK's DDVF-docking site may provide negative feedback to ERK MAPK signaling. |
Co-immunoprecipitation, AlphaFold docking/SLiM prediction, analysis of RSK mutant lacking DDVF-docking site for ERK activation |
bioRxiv (preprint)preprint |
Low |
bio_10.1101_2024.08.08.607128
|
| 2026 |
GAB3 interacts with LYN kinase in lung adenocarcinoma cells to inhibit the MAPK signaling pathway and reverse epithelial-mesenchymal transition (EMT). GAB3 overexpression suppresses LUAD cell proliferation, migration, invasion, and tumor growth. GAB3 also remodels the tumor immune microenvironment by enhancing CXCL10 secretion, increasing CD8+ T cell infiltration and effector function, and sensitizing tumors to anti-PD-1 therapy. |
Co-immunoprecipitation (GAB3-LYN interaction), overexpression and knockdown with MAPK/EMT readouts, in vivo tumor models, immune profiling |
Cancer letters |
Medium |
42031161
|