| 1986 |
FYN (originally named 'syn') was identified as a new member of the protein-tyrosine kinase family, closely related to v-yes and human c-src, encoded on human chromosome 6 with a distinct 2.8-kb transcript. |
Molecular cloning and nucleotide sequence analysis of cDNA |
Proceedings of the National Academy of Sciences of the United States of America |
High |
3526330
|
| 1990 |
Fyn (p59fyn) is physically associated with the PDGF receptor upon PDGF stimulation; Fyn kinase activity is elevated after PDGF stimulation coincident with co-association with the activated receptor. |
Co-immunoprecipitation and kinase activity assay from PDGF-stimulated fibroblasts |
Cell |
High |
1696179
|
| 1990 |
Xenopus laevis possesses fyn genes encoding a protein with 96% amino acid identity to human FYN; fyn transcripts are present in oocytes, implicating multiple Src-family kinases in oogenesis or early development. |
cDNA library screening, sequencing, and Northern blot analysis |
Oncogene |
Medium |
2179818
|
| 1991 |
CD36 (glycoprotein IV) is physically associated with Fyn, Lyn, and Yes protein-tyrosine kinases in human platelets and in GPIV-expressing cell lines, suggesting GPIV ligand interactions activate tyrosine phosphorylation signaling pathways. |
Co-immunoprecipitation from platelet lysates and cell lines |
Proceedings of the National Academy of Sciences of the United States of America |
High |
1715582
|
| 1992 |
Fyn is required for hippocampal long-term potentiation (LTP) and spatial learning; fyn mutant mice show blunted LTP, impaired spatial learning, and increased granule/pyramidal cell numbers in the hippocampus, while src, yes, and abl mutations had no LTP effect. |
Genetic knockout mice, electrophysiology (LTP induction), Morris water maze spatial learning |
Science |
High |
1361685
|
| 1992 |
p21rasGAP associates with Fyn, Lyn, and Yes in thrombin-activated platelets, forming kinase-substrate complexes detectable only after agonist stimulation, positioning Fyn downstream of a G-protein-coupled receptor in platelet signaling. |
Kinase trapping strategy with immunoprecipitation and tyrosine phosphorylation analysis |
The Journal of biological chemistry |
Medium |
1544885
|
| 1995 |
Fyn and Src have both specific and overlapping roles in cytoskeletal regulation: focal adhesion kinase and paxillin hyperphosphorylation is partly dependent on both Src and Fyn in csk-null cells, whereas cortactin and tensin hyperphosphorylation is Src-dependent. Fyn does not rescue the neurulation defect of csk-null mice. |
Genetic epistasis (double mutant analysis in csk-/- src-/- fyn-/- mice) with biochemical tyrosine phosphorylation analysis |
Nature |
High |
7617039
|
| 1996 |
Fyn kinase localizes to the midspace of dividing pro-B cells at anaphase and regulates progression of cytokinesis; fyn-null pro-B cells arrest at late telophase under serum-free conditions, accumulating binucleated cells. |
fyn knockout mice, cell cycle analysis, immunolocalization, morphological analysis |
The Journal of cell biology |
Medium |
8567733
|
| 1998 |
Fyn is N-myristoylated on cytosolic polysomes and then palmitoylated at the plasma membrane; dually acylated Fyn clusters in caveolae-like membrane microdomains and interacts with diverse signaling molecules. |
Biochemical fractionation and acylation analysis |
The international journal of biochemistry & cell biology |
Medium |
9839441
|
| 1998 |
Caveolin-1 functions as a membrane adaptor linking integrin alpha subunits to Fyn; upon integrin ligation, Fyn is activated and binds via its SH3 domain to Shc, leading to Shc Tyr-317 phosphorylation and Grb2 recruitment, coupling integrins to the Ras-ERK pathway for anchorage-dependent cell growth. |
Co-immunoprecipitation, SH3 domain binding assay, mutagenesis, Ras-ERK pathway assay |
Cell |
High |
9741627
|
| 1998 |
CD73-mediated signal transduction in murine splenic T cells requires Fyn; fyn-null mice are unresponsive to CD73 ligation, demonstrating Fyn as a necessary downstream kinase for CD73 signaling. |
fyn-null mice, proliferation assay, IL-2 secretion assay upon CD73 ligation |
European journal of immunology |
Medium |
9808167
|
| 1999 |
Fyn kinase associates with and is maximally active in GPI-anchored protein-containing lipid rafts of oligodendrocytes; Fyn is tightly associated with NCAM 120 and F3 within rafts, and anti-F3 antibody stimulation activates Fyn specifically in rafts. Compartmentation in rafts is prerequisite for F3-Fyn association and kinase activation during myelination. |
Detergent-resistant membrane fractionation, co-immunoprecipitation, kinase activity assay, antibody stimulation |
The Journal of biological chemistry |
High |
10506155
|
| 1999 |
Fyn associates with and dephosphorylates p59 Fyn-binding protein (FYB/ADAP) and Cas in macrophages; these are substrates of YopH (Yersinia phosphatase) whose dephosphorylation disrupts focal complexes and blocks phagocytosis. |
Substrate-trapping immunoprecipitation with inactive YopH, immunolocalization |
Microbial pathogenesis |
Medium |
10502464
|
| 2000 |
Fyn (p59fyn) is an essential upstream kinase in the CD2 signaling pathway; fyn-null T cells show markedly reduced Ca2+ mobilization, MAPK activation, and proliferation in response to CD2 clustering. Fyn-dependent CD2 pathway components include PLC-γ1, Vav, PKC-θ, Dok, FAK, and Pyk2. |
CD2 transgenic fyn-null mice, calcium mobilization, MAPK assay, kinase activity assays, immunoprecipitation |
European journal of immunology |
High |
11093170
|
| 2001 |
Fyn kinase activity (not just Fyn protein) is uniquely required for CNS myelination in the forebrain; a single amino acid substitution abolishing kinase activity causes a myelin deficit as severe as complete Fyn absence. Other Src-family kinases (Src, Yes, Lyn) do not compensate. |
fyn knockout mice, kinase-dead knock-in mice, myelin quantification, oligodendrocyte counting, EM |
The Journal of neuroscience |
High |
11245687
|
| 2001 |
Fyn phosphorylates the NR2B (GluRε2) subunit of NMDA receptors at multiple tyrosines; Tyr-1472 is the major in vivo phosphorylation site, its phosphorylation is greatly reduced in fyn mutant mice, and it is enhanced after hippocampal LTP induction. |
In vitro kinase assay with mutagenesis, co-expression in HEK293, phospho-specific antibody, fyn mutant mice, LTP electrophysiology |
The Journal of biological chemistry |
High |
11024032
|
| 2002 |
Fyn binds Tau via its SH3 domain and binds α-Tubulin via its SH2 and SH3 domains in oligodendrocytes; the Fyn-Tau-microtubule cascade is required for oligodendroglial process outgrowth. Disrupting the Fyn-Tau interaction reduces process number and length. |
Co-immunoprecipitation, dominant-negative competition with Tau deletion mutant, Fumonisin B1 raft disruption, transfection in oligodendroglial cells |
The Journal of neuroscience |
High |
11826099
|
| 2002 |
STEP61, a membrane-associated phosphatase in postsynaptic densities, associates specifically with Fyn and dephosphorylates Fyn at Tyr-420 (activating site) but not Tyr-531, providing a mechanism for reducing Fyn activity in PSDs. STEP61 binds Fyn through its proline-rich and KIM domains; Fyn binds STEP61 through its SH2 domain and Fyn's unique N-terminal domain. |
Substrate-trapping co-transfection in HEK293, reciprocal co-immunoprecipitation, in vitro phosphatase assay with site-specific mutants |
The Journal of biological chemistry |
High |
11983687
|
| 2003 |
Fyn directly binds Nephrin via its SH3 domain and phosphorylates Nephrin on tyrosine residues in podocyte detergent-resistant membranes; Fyn deletion in mice causes coarsening of podocyte foot processes and marked attenuation of Nephrin phosphorylation in glomerular detergent-resistant fractions. |
Co-immunoprecipitation, in vitro direct binding/phosphorylation assay, fyn/yes knockout mice, glomerular fractionation |
The Journal of biological chemistry |
High |
12668668
|
| 2003 |
RACK1 scaffolds Fyn to the NR2B subunit of NMDA receptors specifically in the hippocampus but not cortex; acute ethanol dissociates RACK1 from the complex, facilitating Fyn-mediated NR2B phosphorylation and enhanced channel activity, accounting for hippocampus-selective acute tolerance to ethanol. |
Co-immunoprecipitation from hippocampal vs. cortical tissue, NR2B phosphorylation assay, ethanol treatment, RACK1 dissociation studies |
The Journal of neuroscience |
High |
12736333
|
| 2003 |
In highly metastatic melanoma cells, Fyn is selectively activated among Src-family kinases; Fyn forms a stable complex with cortactin, phosphorylates it, and co-localizes with it at cell membranes, promoting cell migration. Fyn activation occurs downstream of integrin engagement. |
Kinase activity assay, co-immunoprecipitation, immunolocalization, migration assay, integrin stimulation |
The Journal of biological chemistry |
Medium |
13129922
|
| 2003 |
p250GAP, a brain-enriched RhoGAP protein, associates with Fyn in vitro and in vivo and is tyrosine-phosphorylated by Fyn when co-expressed; this phosphorylation is enhanced during oligodendrocyte CG4 cell differentiation, suggesting Fyn regulates RhoGAP activity during oligodendrocyte maturation. |
Co-immunoprecipitation, in vitro kinase assay, co-expression in HEK293T, differentiation model |
Biochemical and biophysical research communications |
Medium |
12788081
|
| 2004 |
Lck and Fyn are segregated into different lipid raft microdomains in unstimulated T cells; Lck activation is upstream of Fyn activation in a unidirectional lck-dependent manner, with their activations being temporally and spatially uncoupled during TCR/CD3 signaling. |
Membrane fractionation, kinase activity assays, T cell receptor stimulation experiments |
Molecular immunology |
Medium |
15220001
|
| 2005 |
Combined absence of Src and Fyn almost abolishes tyrosine phosphorylation of Dab1 and causes a reeler-like phenotype (inverted cortical layering, impaired Purkinje plate), demonstrating that Src and Fyn are redundantly required for Reelin-dependent neuronal positioning in vivo. |
Double knockout mice (src-/-fyn-/-), Dab1 phosphorylation assay, histological brain analysis |
The Journal of neuroscience |
High |
16162939
|
| 2006 |
Crystal structure of the human Fyn kinase domain complexed with staurosporine at 2.8 Å resolution; staurosporine occupies the ATP-binding site with small structural differences from Lck and Csk complexes that may enable selective inhibitor design. |
X-ray crystallography |
Biochemical and biophysical research communications |
High |
16782058
|
| 2006 |
Fyn mediates Semaphorin3A-dependent dendritic spine maturation and PSD-95 cluster formation in cortical neurons; fyn-null neurons bear few dendritic spines, Sema3A does not induce PSD-95 clustering in fyn-null neurons, and double-heterozygous sema3A/fyn mice show reduced spine density. |
fyn-null mice, Sema3A treatment, immunostaining for PSD-95 and NRP-1, PP2 inhibitor, genetic interaction analysis |
The Journal of neuroscience |
High |
16540575
|
| 2006 |
Virus (coxsackievirus) attachment to DAF activates Fyn kinase, which is required for phosphorylation of caveolin and transport of the virus into the cell within caveolar vesicles. A separate Abl/Rac pathway mediates actin rearrangements for viral movement to tight junctions. |
Kinase inhibition, siRNA knockdown, co-immunoprecipitation, viral entry assay, caveolin phosphorylation assay |
Cell |
High |
16413486
|
| 2006 |
Fyn (but not Src) is recruited to early adhesions at the leading edge in response to fibronectin rigidity; this requires Fyn's palmitoylation site. Fyn-dependent phosphorylation of p130Cas at the leading edge mediates the cellular rigidity response and growth. |
Live-cell imaging, GFP fusion proteins, palmitoylation mutant, p130Cas phosphorylation assay, spreading/growth assays |
Molecular biology of the cell |
Medium |
16597701
|
| 2006 |
Crystal structure of HIV-1 Nef conserved core complexed with a mutant Fyn SH3 domain (R96I) shows that the Nef PxxP motif forms a polyproline type II helix engaging the SH3 domain; this reveals how high-affinity and specificity is achieved in the Nef-SH3 interaction. |
X-ray crystallography of Nef–Fyn SH3 complex |
Cell |
High |
8681387
|
| 2007 |
Oxidant-mediated Fyn kinase activation leads to secondary activation of the c-Cbl ubiquitin ligase, causing specific reduction of c-Cbl target PDGFRα and other RTKs (but not TrkC), thereby suppressing mitogenic signaling in CNS progenitor cells at environmentally relevant toxicant levels. |
In vitro and in vivo Fyn kinase activation assay, c-Cbl ubiquitin ligase activity, RTK level quantification, toxicant treatment |
PLoS biology |
Medium |
17298174
|
| 2007 |
Unc119 interacts with and activates Fyn; Unc119 is required for TGF-β/PDGF-induced Fyn phosphorylation. Unc119-induced myofibroblast differentiation (α-SMA induction) requires Fyn and the p38 MAPK pathway; Unc119 overexpression does not stimulate α-SMA in SYF cells unless Fyn is restored. |
Co-immunoprecipitation, co-localization, kinase activity assay, SYF reconstitution, siRNA, p38 inhibition |
Journal of immunology |
Medium |
17579091
|
| 2008 |
Activated Fyn phosphorylates hnRNP A2 in oligodendrocytes; L1 neuronal adhesion molecule binding activates Fyn, increasing hnRNP A2 phosphorylation and stimulating localized translation of MBP mRNA at axon-glia contact sites. |
Phosphorylation assay, L1-Fc stimulation, reporter construct translation assay, hnRNP A2 immunoprecipitation from oligodendrocytes |
The Journal of cell biology |
High |
18490510
|
| 2008 |
Murine gammaherpesvirus M2 protein is phosphorylated by Fyn at Tyr-120 and Tyr-129 in non-hematopoietic cells; phospho-Tyr-120 creates docking sites for Vav1 and Fyn SH2 domains, enabling trimolecular Fyn/M2/Vav1 complex formation that activates Vav1/Rac1 pathway for B-cell latency establishment. |
In vivo phosphorylation analysis, SH2 domain binding assay, co-immunoprecipitation, viral mutant infection in mice |
PloS one |
Medium |
18301737
|
| 2008 |
Fyn deficiency in zebrafish (along with Yes) causes convergent-extension cell movement defects; comparative phosphoproteomics of Fyn/Yes morphant embryos identifies adducin and PDLIM5 phosphorylation changes, implicating Fyn/Yes in regulating signaling pathways controlling gastrulation movements. |
Morpholino knockdown in zebrafish, quantitative phosphoproteomics with stable isotope labeling, LC-MS/MS |
Molecular & cellular proteomics |
Medium |
18550893
|
| 2008 |
Fyn kinase is required for meiotic maturation in mouse oocytes; FYN siRNA knockdown and FYN-null oocytes show ~50% reduction in progression to metaphase-II, with meiotic spindle and chromosome alignment defects. |
siRNA knockdown, fyn-null mice, in vitro and in vivo oocyte maturation, SKI606 inhibitor treatment |
Developmental biology |
Medium |
19118543
|
| 2009 |
Fyn specifically regulates endocytosis of flotillin-1 and flotillin-2 by directly phosphorylating Tyr-160 of flotillin-1 and Tyr-163 of flotillin-2; these phosphorylations are required for flotillin internalization and uptake of the GPI-linked protein CD59. |
SYF cell reconstitution with individual Src kinases, active Fyn overexpression, rapamycin-inducible Fyn dimerization system, site-directed mutagenesis, endocytosis assays |
Journal of cell science |
High |
19258392
|
| 2009 |
An integrin/contactin complex on oligodendrocytes integrates signals by differential Fyn phosphorylation: integrin induces dephosphorylation of inhibitory Tyr-531, while contactin increases phosphorylation of both Tyr-531 and activating Tyr-420; combined effect enhances Fyn activity and regulates oligodendrocyte survival and myelination. |
siRNA knockdown, L1-Fc stimulation, phospho-specific western blot for Tyr-531 and Tyr-420, myelination co-culture assay |
The Journal of neuroscience |
High |
19625508
|
| 2009 |
Laminin promotes oligodendrocyte differentiation via Fyn activation; in laminin-deficient brains, Fyn activity is suppressed and levels of negative regulators Csk and Cbp are elevated, indicating that laminin modulates Fyn activity via its regulatory proteins. |
fyn KO mice, laminin-deficient (dy/dy) mice, Src kinase activity assay, western blotting for Csk/Cbp |
The Journal of neuroscience |
Medium |
19776266
|
| 2009 |
Srcasm promotes Fyn kinase down-regulation in a phosphorylation-dependent manner requiring Fyn kinase activity, Srcasm phosphorylation, and the Srcasm GAT domain, acting as a molecular rheostat for activated Fyn in keratinocytes. |
K14-Fyn transgenic mice, K14-Fyn/Srcasm double transgenic mice, biochemical kinase level analysis, phosphorylation-null mutant |
Cancer research |
Medium |
19934324
|
| 2010 |
Fyn is recruited to the cortex overlying chromosomes and co-localizes with F-actin during meiotic and mitotic cleavage furrow ingression in mouse oocytes; dominant-negative Fyn prolongs furrow ingression duration and impairs polar body extrusion, implicating Fyn in actin cytoskeletal regulation during cell division. |
Live-cell confocal imaging, microinjection of Fyn cRNAs (wild-type, dominant-negative), SU6656 inhibitor treatment |
Reproduction |
Medium |
20841362
|
| 2010 |
Fyn-null female mice exhibit reduced fertility; Fyn-null oocytes show higher frequency of spindle/chromosome abnormalities and 24% failure of pronuclear congression, with altered protein tyrosine phosphorylation patterns attributed to actin cytoskeletal defects rather than calcium signaling. |
fyn knockout mice, oocyte maturation assays, fertilization assays, phosphotyrosine western blot, morphological analysis |
Reproduction, fertility, and development |
Medium |
20591331
|
| 2011 |
Fyn requires HnRNPA2B1 and Sam68 to coordinate apoptosis regulation in pancreatic cancer; Fyn activity regulates HnRNPA2B1 expression (affecting Bcl-xS formation) and phosphorylates Sam68 (affecting Bcl-xL formation), with the two pathways cooperating to control cell survival. |
Kinase-dead Fyn, RNAi knockdown, Bcl-x splicing assay, apoptosis assay, co-immunoprecipitation |
Carcinogenesis |
Medium |
21642356
|
| 2011 |
Fyn regulates the Th17/Treg balance by controlling RORγt upregulation kinetics and STAT3 activation; fyn-null CD4+ T cells under Th17-skewing conditions show decreased IL-17, increased Foxp3, delayed Il23r and Irf4 upregulation, and aberrant Socs3 expression, reducing Th17 cells in vivo. |
fyn knockout mice, Th17 polarization cultures, intracellular cytokine staining, T cell transfer to Rag1-/- hosts |
Journal of immunology |
Medium |
22539787
|
| 2012 |
Fyn is required for meiosis resumption in mouse oocytes; Fyn localizes to the oocyte cortex and spindle poles, is recruited to the contractile ring during polar body extrusion, and undergoes proteasome-independent degradation during GVBD. Dominant-negative Fyn or SU6656 inhibits GVBD and polar body extrusion. |
Immunostaining, live confocal imaging, dominant-negative microinjection, SU6656 inhibitor, western blot |
Cell cycle |
Medium |
20372074
|
| 2012 |
Fyn kinase deficiency in male mice causes high frequency of abnormal sperm morphology and reduced acrosome reaction capacity; Fyn-null sperm have slightly modified capacitation-associated tyrosine phosphorylation, suggesting Fyn functions in acrosome shaping within the testis. |
fyn knockout mice, artificial insemination competition, morphological analysis, acrosome reaction assay, tyrosine phosphorylation western blot |
Biology of reproduction |
Medium |
21918125
|
| 2013 |
mGluR5 is a co-receptor coupling Aβ oligomer-PrPC complexes to Fyn kinase activation; PrPC and mGluR5 interact physically, and cytoplasmic Fyn forms a complex with mGluR5. Aβo-PrPC-mGluR5 signaling activates Fyn, mediates eEF2 phosphorylation and dendritic spine loss. |
Co-immunoprecipitation, Xenopus oocyte calcium assay, neuronal calcium imaging, dendritic spine counting, mGluR5 antagonist rescue in AD transgenic mice |
Neuron |
High |
24012003
|
| 2014 |
FYN directly phosphorylates COX2 at Tyr-446; a phospho-mimetic COX2 mutation (Y446E) promotes COX2 enzymatic activity while a phosphorylation-blocking mutation (Y446F) prevents FYN-mediated COX2 activation, establishing post-translational regulation of COX2 by FYN. |
Co-immunoprecipitation, in vitro kinase assay, phospho-mimetic and blocking mutagenesis, COX2 activity assay |
Oncotarget |
High |
24970799
|
| 2014 |
FYN mutations are recurrently found in peripheral T cell lymphomas (PTCL), implicating Src signaling in PTCL pathogenesis. The mutations were identified by whole-exome sequencing and targeted deep sequencing. |
Whole-exome sequencing, RNA sequencing, targeted deep sequencing of tumor-normal pairs |
Nature genetics |
Low |
24413734
|
| 2015 |
Fyn inhibition with AZD0530 prevents Aβo-induced Fyn signaling and downstream phosphorylation of Pyk2 and NR2B in brain slices; treatment of APP/PS1 transgenic mice rescues spatial memory deficits, synaptic depletion, microglial activation, and Tau phosphorylation abnormalities without altering APP/Aβ metabolism. |
Brain slice phosphorylation assays, Morris water maze, novel object recognition, immunohistochemistry, APP/PS1/Tau transgenic mice, AZD0530 pharmacological inhibition |
Annals of neurology |
High |
25707991
|
| 2015 |
BDNF activates Fyn phosphorylation in oligodendrocytes via TrkB; Fyn acts as an intermediate kinase phosphorylating Erk1/2 downstream of BDNF-TrkB, promoting myelination. Kinase-dead Fyn abolishes BDNF-induced Erk1/2 activation and myelination, and Fyn overexpression mimics BDNF effects. |
Kinase-dead Fyn overexpression, PP2 inhibition, myelinating co-cultures, Erk1/2 phosphorylation assay, TrkB dependency analysis, in vivo colocalization |
Glia |
High |
26449489
|
| 2015 |
Fyn-phosphorylated PIKE-A binds to the AMPK catalytic α subunit and impairs T172 phosphorylation, blocking AMPK kinase activity and its tumor-suppressive actions; depletion of Fyn or mutation of Fyn phosphorylation sites on PIKE-A abolishes PIKE-A/AMPK association. |
Co-immunoprecipitation, in vitro kinase assay, Fyn depletion by shRNA, pharmacological inhibition, AMPK T172 phosphorylation assay, oncogenic assays |
Cell death and differentiation |
Medium |
26001218
|
| 2015 |
Thy-1 physically couples to inactive αvβ3 integrin via its RGD-like motif; this coupling facilitates membrane raft/Src family kinase pre-adhesion clustering. Loss of Thy-1 impairs Fyn recruitment to adhesion complexes, mechanosensitive Rho signaling, and rigidity sensing in fibroblasts. |
Co-immunoprecipitation, proximity ligation assay, Fyn recruitment imaging, Rho signaling assay, traction force microscopy |
The Journal of cell biology |
Medium |
26459603
|
| 2016 |
FYN interacts with the C-terminal domain of NOX4 in cardiomyocytes; FYN directly phosphorylates NOX4 at Tyr-566, negatively regulating NOX4-induced superoxide production and apoptosis. FYN-deficient mice show exacerbated cardiac hypertrophy, dysfunction, and increased ROS; deletion of Nox4 rescues LV remodeling in FYN-deficient mice. |
Co-immunoprecipitation, in vitro phosphorylation assay, Y566 mutagenesis, fyn-/- and nox4-/- mice, cardiac function measurements, ROS assay |
The Journal of clinical investigation |
High |
27525436
|
| 2016 |
Fyn-dependent phosphorylation of SHP-1 at serine-591 inactivates the phosphatase, enabling activatory immunoreceptor signaling; in contrast, Lyn phosphorylates SHP-1 Tyr-536 to activate it and promote inhibitory signaling. Fyn deficiency is protective in nephritis and arthritis mouse models. |
Phosphorylation site mutagenesis, fyn and lyn knockout mice, nephritis/arthritis mouse models, SHP-1 phosphatase activity assay |
Nature communications |
High |
28811476
|
| 2016 |
MOBP synthesis in oligodendrocytes is stimulated by Fyn activity; MOBP promotes oligodendroglial morphological differentiation, identifying MOBP as a downstream effector of Fyn-regulated myelin protein synthesis. |
Fyn kinase inhibition/activation in cultured primary oligodendrocytes, MOBP knockdown, morphological analysis |
Journal of cell science |
Medium |
26801084
|
| 2016 |
CD36 nanoclusters are enriched with Fyn at baseline; exposure to multivalent ligands (TSP-1 or anti-CD36 IgM) enhances CD36 clustering and activates Fyn without altering Fyn enrichment at nanoclusters, demonstrating that cluster compaction/growth is the activating signal. |
Quantitative multi-channel high- and super-resolution imaging, pharmacological perturbation, Fyn activation assay |
Journal of cell science |
Medium |
27694211
|
| 2017 |
PTPN23 normally suppresses FYN activity in mammary epithelial cells; PTPN23 depletion causes hyperphosphorylation of FYN autophosphorylation site and Tyr-142 of β-catenin. Double knockout of FYN and PTPN23 attenuates tumor outgrowth, establishing PTPN23 as a key phosphatase suppressing FYN in breast tumorigenesis. |
PTPN23 knockdown, orthotopic transplantation mouse model, FYN/PTPN23 CRISPR/Cas9 double KO, xenograft model, AZD0530 treatment |
Genes & development |
High |
29066500
|
| 2018 |
Fyn directly phosphorylates β-catenin at Tyr-142, stabilizing β-catenin and promoting its nuclear translocation in chondrocytes; Fyn-null mice are protected from post-traumatic and age-dependent osteoarthritis, and Fyn inhibitors block β-catenin pathway activation and ECM catabolic enzymes. |
In vitro kinase assay, Tyr-142 phosphorylation analysis, β-catenin nuclear translocation assay, fyn-knockout OA mouse model, Fyn inhibitor treatment |
Annals of the rheumatic diseases |
High |
29555825
|
| 2018 |
Fyn participates in EPO receptor signaling; fyn-null mice exhibit reduced Tyr-phosphorylation of EPO-R and decreased STAT5 activity. Fyn is also a physiologic repressor of Nrf2; absence of Fyn results in persistent Nrf2 activation and over-activation of Jak2-Akt-mTOR pathway in erythroblasts. |
fyn-knockout mice, EPO-R phosphorylation assay, STAT5 activity assay, Nrf2 activation analysis, Jak2-Akt-mTOR pathway western blot, rapamycin rescue |
American journal of hematology |
Medium |
30252956
|
| 2018 |
SHROOM3 interacts with FYN via a critical SH3-binding domain (distinct from its ROCK-binding domain) in human podocytes; this interaction activates Fyn kinase and is required for downstream nephrin phosphorylation. Shroom3 knockdown in mice induces albuminuria with foot process effacement. |
Co-immunoprecipitation with endogenous proteins, SH3-binding domain mutagenesis, Shroom3 knockdown mice, nephrin phosphorylation assay, electron microscopy |
Journal of the American Society of Nephrology |
High |
30341149
|
| 2019 |
Frontotemporal dementia P301L mutant Tau immobilizes Fyn in dendritic spines, altering its motion state distribution and nanoclustering; wild-type Tau removal increases Fyn mobility in dendritic shafts, demonstrating that Tau controls the nanoscale organization of Fyn in neuronal dendrites. |
Single-molecule tracking in mouse hippocampal neurons, Tau knockout/overexpression, P301L Tau expression |
eLife |
High |
31237563
|
| 2019 |
Fyn kinase activity is localized at plasma membrane microdomains, with its submembrane localization providing a suppressive microenvironment; Fyn localized outside its microdomains shows hyperactivity, and relatively high Fyn activity is observed in perinuclear regions. |
FRET biosensor in live cells, membrane microdomain targeting with different lipid anchor motifs, growth factor stimulation |
ACS sensors |
Medium |
30588803
|
| 2022 |
Fyn and TOM1L1 are recruited to a subset of clathrin-coated pits (CCPs) with unique lifetimes; Fyn and TOM1L1 perturbation impairs EGF-stimulated Akt2 (but not Akt1) phosphorylation and mediates TOM1L1/Fyn-dependent SHIP2 recruitment to CCPs, linking clathrin-coated pits to specific Akt isoform signaling. |
Live-cell imaging, siRNA knockdown, phospho-Akt isoform analysis, SHIP2 recruitment assay |
The Journal of cell biology |
Medium |
35238864
|
| 2023 |
FYN directly binds to TOPK/PBK in gastric cancer cells and phosphorylates TOPK at Tyr-272; TOPK-Y272F mutation impairs FYN-TOPK interaction and abolishes TOPK phosphorylation. Phosphorylated TOPK in turn controls HSPB1 and p-HSPB1(Ser15) levels, promoting gastric cancer proliferation and metastasis. |
Co-IP, pull-down, immunofluorescence co-localization, 32P-labeled isotope kinase assay, in vitro kinase assay, phospho-specific antibody generation, TOPK knockout mice, phosphoproteomics |
Journal of experimental & clinical cancer research |
High |
37016377
|