ArticlePloS one2011
The adaptor protein SH2B3 (Lnk) negatively regulates neurite outgrowth of PC12 cells and cortical neurons.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- The cellular model for Alzheimer's disease research: PC12 cells.Frontiers in molecular neuroscience · 2022Pooled it
- Bioinformatic Analyses of the Ataxin-2 Family Since Algae Emphasize Its Small Isoforms, Large Chimerisms, and the Importance of Human Exon 1B as Target of Therapies to Prevent Neurodegeneration.International journal of molecular sciences · 2026Article
- The LNK adaptor protein: a dual regulator of proliferation and migration in solid tumors.Molecular & cellular oncology · 2026Review
- Astrocyte activation persists one year after TBI: a dynamic shift from inflammation to neurodegeneration.Communications biology · 2025Article
- A foundation model for learning genetic associations from brain imaging phenotypes.Bioinformatics advances · 2025Article
- Modulation of JAK-STAT Signaling by LNK: A Forgotten Oncogenic Pathway in Hormone Receptor-Positive Breast Cancer.International journal of molecular sciences · 2023Review
- The nucleolar δ isoform of adapter protein SH2B1 enhances morphological complexity and function of cultured neurons.Journal of cell science · 2022Article
- The Role of LNK (SH2B3) in the Regulation of JAK-STAT Signalling in Haematopoiesis.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Assessment of differentially methylated loci in individuals with end-stage kidney disease attributed to diabetic kidney disease: an exploratory study.Clinical epigenetics · 2021Article
- Phosphorylation of the Unique C-Terminal Tail of the Alpha Isoform of the Scaffold Protein SH2B1 Controls the Ability of SH2B1α To Enhance Nerve Growth Factor Function.Molecular and cellular biology · 2018Article
- The role of LNK/SH2B3 genetic alterations in myeloproliferative neoplasms and other hematological disorders.Leukemia · 2017Review
- The Dyslexia-susceptibility Protein KIAA0319 Inhibits Axon Growth Through Smad2 Signaling.Cerebral cortex (New York, N.Y. : 1991) · 2017Article
- The role of small adaptor proteins in the control of oncogenic signalingr driven by tyrosine kinases in human cancer.Oncotarget · 2016Review
- SH2B1 and IRSp53 proteins promote the formation of dendrites and dendritic branches.The Journal of biological chemistry · 2015Article
- 12q24 locus association with type 1 diabetes: SH2B3 or ATXN2?World journal of diabetes · 2014Review
- Differentially methylated regions in maternal and paternal uniparental disomy for chromosome 7.Epigenetics · 2014Article
- SH2B1β interacts with STAT3 and enhances fibroblast growth factor 1-induced gene expression during neuronal differentiation.Molecular and cellular biology · 2014Article
- Review
- Tolerance of neurite outgrowth to Rho kinase inhibitors decreased by cyclooxygenase-2 inhibitor.Neural regeneration research · 2012Article
- Adaptor protein LNK is a negative regulator of brain neural stem cell proliferation after stroke.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SH2B adaptor protein family members (SH2B1-3) regulate various physiological responses through affecting signaling, gene expression, and cell adhesion. SH2B1 and SH2B2 were reported to enhance nerve growth factor (NGF)-induced neuronal differentiation in PC12 cells, a well-established neuronal model system. In contrast, SH2B3 was reported to inhibit cell proliferation during the development of immune system. No study so far addresses the role of SH2B3 in the nervous system. In this study, we provide evidence suggesting that SH2B3 is expressed in the cortex of embryonic rat brain. Overexpression of SH2B3 not only inhibits NGF-induced differentiation of PC12 cells but also reduces neurite outgrowth of primary cortical neurons. SH2B3 does so by repressing NGF-induced activation of PLCγ, MEK-ERK1/2 and PI3K-AKT pathways and the expression of Egr-1. SH2B3 is capable of binding to phosphorylated NGF receptor, TrkA, as well as SH2B1β. Our data further demonstrate that overexpression of SH2B3 reduces the interaction between SH2B1β and TrkA. Consistent with this finding, overexpressing the SH2 domain of SH2B3 is sufficient to inhibit NGF-induced neurite outgrowth. Together, our data demonstrate that SH2B3, unlike the other two family members, inhibits neuronal differentiation of PC12 cells and primary cortical neurons. Its inhibitory mechanism is likely through the competition of TrkA binding with the positive-acting SH2B1 and SH2B2.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.