| 2007 |
SH2B2beta, a splice isoform of SH2B2 lacking an SH2 domain, binds to SH2B1 and SH2B2alpha via its dimerization (DD) domain (demonstrated by GST pulldown in vitro and co-immunoprecipitation in intact cells), and markedly attenuates SH2B1-promoted JAK2 activation and subsequent IRS-1 tyrosine phosphorylation, as well as SH2B1- or SH2B2alpha-promoted insulin signaling, acting as an endogenous inhibitor. |
GST fusion protein pulldown (in vitro), co-immunoprecipitation in intact cells, functional kinase/phosphorylation assays |
Endocrinology |
High |
17204555
|
| 2013 |
Deletion of liver SH2B1 in SH2B2 null mice attenuated VLDL secretion, and adult-onset deletion of hepatic SH2B1 (alone) decreased DGAT2 expression and increased ATGL expression, indicating that SH2B1 and SH2B2 together regulate hepatic triglyceride synthesis, lipolysis, and VLDL secretion without affecting insulin sensitivity or glucose metabolism. |
Hepatocyte-specific SH2B1 knockout combined with whole-body SH2B2 knockout mice; metabolic phenotyping, gene expression analysis (qRT-PCR/Western blot) |
PloS one |
Medium |
24358267
|
| 2021 |
SH2B2 participates in insulin receptor signaling by being phosphorylated downstream of the activated insulin receptor, initiating activation of G proteins such as TC10 (via the c-Cbl/CAP/TC10 pathway). |
Review synthesizing prior experimental work on insulin receptor signaling pathways |
The Journal of clinical investigation |
Low |
33393497
|
| 2013 |
The SH2 domain of SH2B2 (APS) binds to phosphorylated tyrosines in the insulin receptor activation loop (engaging two phosphotyrosines via a dimeric SH2 domain interaction), providing a docking site for this adaptor protein. |
Structural and biochemical characterization reviewed; dimeric SH2 domain engagement of two phosphotyrosines in activation loop described from prior structural studies |
Cold Spring Harbor perspectives in biology |
Medium |
23457259
|
| 2014 |
SH2B2 (APS) forms homo- or heterodimers with SH2B1 via N-terminal dimerization domains; its SH2 domain binds tyrosyl-phosphorylated proteins including JAK2, insulin receptors, IGF-1 receptors, IRS-1, and IRS-2. Unlike SH2B1, SH2B2 is not required for maintenance of normal energy and glucose homeostasis (SH2B2 knockout mice are metabolically normal). |
Genetic knockout mouse studies; biochemical binding assays (co-IP, domain analysis) synthesized from prior work |
World journal of diabetes |
Medium |
25126397
|
| 2011 |
SH2B2 (APS) enhances NGF-induced neuronal differentiation in PC12 cells; SH2B3 competes with SH2B2 for TrkA binding to inhibit this effect, as overexpression of the SH2 domain of SH2B3 reduces SH2B1β-TrkA interaction and inhibits NGF-induced neurite outgrowth. |
Overexpression studies in PC12 cells, co-immunoprecipitation of TrkA binding, neurite outgrowth assays |
PloS one |
Medium |
22028877
|
| 2009 |
Nuclear translocation of SH2B2 (APS) was not observed, in contrast to SH2B1β which shuttles between plasma membrane and nucleus; SH2B2 lacks nuclear localization/export signal-dependent nucleocytoplasmic shuttling function. |
Live imaging and localization studies of SH2B family members in cells; comparison of SH2B1β and SH2B2 subcellular localization |
Molecular endocrinology |
Medium |
19372237
|
| 2024 |
In Aps/Sh2b2-deficient mice, GC B cell numbers are reduced after immunization and cell death of Aps−/− GC B cells is enhanced compared to wild-type. IgE-specific production is impaired. Furthermore, Aps deficiency in B cells results in augmented depletion of IgE+ blasts by B cell receptor crosslinking (anti-CD79b), suggesting SH2B2/APS promotes survival of GC B cells and IgE+ plasma cells downstream of BCR signaling. |
Genetic knockout mice (Aps−/−), in vivo immunization, flow cytometry for GC B cell frequencies/apoptosis, in vitro B cell culture system with BCR crosslinking |
Scientific reports |
Medium |
39090233
|
| 2025 |
SH2B2 is downregulated in MPTP-induced mouse PD model and MPP+-treated SH-SY5Y cells; overexpression of SH2B2 reversed MPP+-induced cell viability reduction and apoptosis in SH-SY5Y cells, upregulated tyrosine hydroxylase (TH) expression, downregulated IBA1 levels (neuroinflammation marker), and improved motor function in MPTP mice, indicating a neuroprotective role for SH2B2 in dopaminergic neurons. |
In vivo MPTP mouse model with lentiviral SH2B2 overexpression; in vitro MPP+-treated SH-SY5Y cells with OE-SH2B2; behavioral tests, CCK-8 viability assay, flow cytometry (apoptosis), Western blot, IHC |
Neuroscience |
Medium |
41482210
|