| 1994 |
DEP-1 (PTPRJ) was cloned as a receptor-like protein tyrosine phosphatase with an extracellular segment containing eight fibronectin type III repeats, a single transmembrane segment, and a single intracellular PTP domain; PTP activity was demonstrated in immunocomplexes, and expression was dramatically increased in dense cell cultures relative to sparse cultures, suggesting a role in contact inhibition of cell growth. |
cDNA cloning, immunoprecipitation PTP activity assay, immunoblot analysis of endogenous DEP-1 in WI-38 fibroblasts at varying cell densities |
Proceedings of the National Academy of Sciences of the United States of America |
High |
7937872
|
| 2000 |
DEP-1 dephosphorylates the PDGF beta-receptor in a site-selective manner: preferred site is pY1021 and poorly preferred sites include pY857 and pY562; selectivity is determined by the primary amino acid sequence surrounding each phosphorylation site, with basic residues at positions -4 and +3 reducing dephosphorylation efficiency. DEP-1–PDGF beta-receptor complexes were detected in DEP-1-inducible cells. |
Inducible DEP-1 expression cell line, in vitro dephosphorylation of PDGF beta-receptor, phosphopeptide mapping, co-immunoprecipitation |
The Journal of biological chemistry |
High |
10821867 12062403
|
| 2001 |
An extracellular ligand present in Matrigel upregulates the specific catalytic activity of DEP-1; the effect requires the DEP-1 extracellular domain (ECD), as a truncated DEP-1 lacking most of the ECD fails to respond, and soluble ECD blocks the activity increase, providing the first evidence for upregulation of a receptor-like PTP specific activity by extracellular ligands. |
Matrigel stimulation of cells, immunoprecipitation PTP activity assay, ECD-deletion mutant and soluble ECD competition experiments |
Oncogene |
Medium |
11526512
|
| 2002 |
DEP-1 uses substrate-trapping to interact with and dephosphorylate the HGF receptor Met and the adaptor Gab1; DEP-1 preferentially dephosphorylates Gab1-binding pY1349 and morphogenesis-related pY1365 on Met, while activation-loop tyrosines Y1230/1234/1235 are not preferred targets, indicating substrate specificity that modulates Met signaling quality rather than simply turning it off. |
Substrate-trapping mutant (maltose-binding protein fusion), co-immunoprecipitation in 293 cells expressing CSF-Met chimera, in vitro dephosphorylation with site mapping |
The Journal of biological chemistry |
High |
12475979
|
| 2002 |
DEP-1 substrate-trapping mutants interact specifically with p120 catenin (p120ctn), beta-catenin, and gamma-catenin; DEP-1 is concentrated at cell-cell contacts in A549 cells where it colocalizes with p120ctn, suggesting a role in adherens junction regulation. |
GST-fusion substrate-trapping pulldown with D/A mutant catalytic domain, co-localization by immunofluorescence |
Oncogene |
Medium |
12370829
|
| 2003 |
DEP-1/CD148 is required for contact inhibition of VEGF-induced endothelial cell proliferation: a dominant-negative DEP-1 mutant and RNAi-mediated DEP-1 knockdown both partially restored VEGFR-2 phosphorylation and MAP kinase activation that were suppressed by VE-cadherin–beta-catenin complex at junctions, placing DEP-1 as a junctional phosphatase that inactivates VEGFR-2 upon VEGF stimulation in confluent cells. |
Dominant-negative mutant overexpression, RNA interference, co-immunoprecipitation of VEGFR-2 with VE-cadherin complex, comparison of isogenic VE-cadherin-null vs. expressing cells |
The Journal of cell biology |
High |
12771128
|
| 2003 |
Homozygous knock-in mice expressing a catalytically inactive CD148 allele (CD148ΔCyGFP) die at mid-gestation (before E11.5) with vascularization failure: enlarged primitive vessels, increased endothelial mitosis, defective vascular remodeling/branching, impaired pericyte investment, and defective endocardial cushion formation, demonstrating that CD148 phosphatase activity is required for developmental vascular organization and regulation of endothelial proliferation. |
Gene targeting (knock-in of GFP replacing cytoplasmic domain), embryo phenotyping, immunostaining for endothelial markers |
Molecular and cellular biology |
High |
12588999
|
| 2003 |
CD148 is excluded from the immunological synapse via its extracellular domain, limiting its access to TCR-proximal substrates; targeting the CD148 phosphatase domain to the synapse potently inhibited NFAT activation induced by all TCR triggers, whereas physiological CD148 only inhibited responses to soluble anti-TCR but not to APC-presented antigens, establishing that ectodomain-mediated spatial exclusion regulates CD148 function in T cells. |
Tetracycline-inducible CD148 expression in Jurkat, immunofluorescence microscopy, targeted chimeric constructs, NFAT-luciferase reporter |
The Journal of cell biology |
High |
12913111
|
| 2001 |
Overexpression of CD148 in Jurkat T cells inhibited TCR-mediated NFAT activation, Ras pathway, and calcium pathway in a phosphatase-activity-dependent manner; downstream analysis revealed that PLCgamma1 and LAT were strikingly hypophosphorylated upon TCR stimulation in CD148-expressing cells, while Slp-76 and Itk were modestly reduced, placing CD148-mediated dephosphorylation upstream of the Ras and calcium branches of TCR signaling. |
Tetracycline-inducible expression of WT and phosphatase-dead CD148 in Jurkat, NFAT reporter assay, phosphotyrosine immunoblotting, calcium mobilization assay |
Molecular and cellular biology |
High |
11259588
|
| 2008 |
CD148 loss-of-function mice showed hyperphosphorylation of the C-terminal inhibitory tyrosine of Src family kinases (SFKs) in B cells and macrophages, and CD148/CD45 double-deficient cells exhibited more severe defects than either single knockout, establishing that CD148 positively regulates SFKs (by dephosphorylating their inhibitory C-terminal tyrosine) in B cells and macrophages and is partially redundant with CD45. |
CD148 conditional knockout mice, CD148/CD45 double knockout mice, phospho-specific immunoblotting for SFK C-terminal inhibitory tyrosine, B and myeloid lineage functional assays |
Immunity |
High |
18249142
|
| 2008 |
DEP-1 dephosphorylates tyrosines in the VEGFR2 kinase activation loop (reducing all major autophosphorylation sites upon DEP-1 depletion); surprisingly, DEP-1 depletion increased phosphorylation of Src inhibitory Y529, impairing Src and Akt activation. Mechanistically, DEP-1 dephosphorylates Src inhibitory Y529 (activating Src), which promotes Gab1 phosphorylation and PI3K–Akt signaling needed for endothelial cell survival. |
siRNA knockdown, catalytically inactive DEP-1 expression, phospho-specific immunoblotting, Src-Y529F rescue experiment, Gab1 co-immunoprecipitation with PI3K |
Molecular and cellular biology |
High |
18936167
|
| 2009 |
DEP-1 physically associates with EGFR at the cell surface and dephosphorylates it, stabilizing EGFR by preventing CBL-GRB2 ubiquitin ligase complex association and subsequent endosomal sorting/degradation; DEP-1 remains confined to the cell surface while activated EGFR undergoes endocytosis, demonstrating bidirectional enzyme–substrate interaction with spatial segregation. |
siRNA screen of all human tyrosine phosphatases (unbiased), co-immunoprecipitation, phosphorylation and ubiquitination assays, confocal imaging of EGFR trafficking |
Current biology : CB |
High |
19836242
|
| 2009 |
DEP-1 directly dephosphorylates ERK1/2 at phosphotyrosine Y204 (activation loop); DEP-1 contains a KIM-like motif that recruits ERK1/2 via the ERK common docking domain, and ERK mutants in the docking domain are insensitive to DEP-1 dephosphorylation. DEP-1 modulates ERK phosphorylation downstream of MEK without affecting MEK activity. |
High-density peptide array substrate screen, pulldown assays, in vitro dephosphorylation, site-directed mutagenesis of ERK docking domain, EGF stimulation with DEP-1 concentration variation |
The Journal of biological chemistry |
High |
19494114
|
| 2009 |
CD148 is essential for platelet activation and arterial thrombosis: CD148-deficient mice exhibit a bleeding tendency, and their platelets show markedly reduced basal SFK activity, resulting in global hyporesponsiveness to agonists signaling through SFKs (collagen, fibrinogen) as well as modestly reduced responses to thrombin, identifying CD148 as the only receptor-like PTP in platelets and a global positive regulator of SFK activity. |
CD148 knockout mice, tail-bleeding assay, in vivo arterial thrombosis model, SFK phosphorylation immunoblotting, platelet aggregation and secretion assays |
Blood |
High |
19246339
|
| 2008 |
CD148 interacts with and dephosphorylates p85, the regulatory subunit of PI3K, when p85 is tyrosine-phosphorylated (e.g., by active Src); co-expression of CD148 reduced p85 phosphorylation and attenuated PI3K activity upon serum stimulation, while CD148 knockdown increased PI3K activity, demonstrating CD148 as a direct negative regulator of PI3K via p85 dephosphorylation. |
Yeast two-hybrid with substrate-trapping mutant bait, co-immunoprecipitation in cells, in vitro dephosphorylation of p85, PI3K activity assay, siRNA knockdown |
The Biochemical journal |
High |
18348712
|
| 2011 |
DEP-1 is a direct negative regulator of FLT3 signaling: substrate-trapping mutants (D1205A, C1239S) co-immunoprecipitated with FLT3, recombinant DEP-1 dephosphorylated activated FLT3 in vitro, and DEP-1 depletion caused site-selective hyperphosphorylation of FLT3 pY589, pY591, pY842. DEP-1 loss enhanced FLT3-dependent ERK activation and cell proliferation. |
Substrate-trapping co-IP, in vitro dephosphorylation, shRNA knockdown in 32D myeloid cells and THP-1, overexpression in 32D and HEK293 |
The Journal of biological chemistry |
High |
21262971
|
| 2012 |
FLT3 ITD causes oxidative inactivation of DEP-1 through reactive oxygen species (ROS)-mediated oxidation of the DEP-1 catalytic cysteine; FLT3 ITD kinase inhibition or NADPH-oxidase inhibition reactivated DEP-1. RNAi-mediated DEP-1 depletion partially abrogated the inhibitory effects of ROS quenching on FLT3 ITD cell transformation, establishing a DEP-1-dependent mechanism of ROS-mediated oncogenesis. |
DEP-1 activity assay with oxidation controls, FLT3 inhibitor treatment, NADPH-oxidase inhibition, catalase/Prx-1 overexpression, RNAi knockdown, mouse model with Prx-1 overexpression |
Blood |
High |
22438257
|
| 2011 |
Syndecan-2 extracellular domain (S2ED) is a novel ligand for CD148; the region proximal to the transmembrane domain of syndecan-2 is the site of interaction with CD148; CD148 acts as a key intermediary between syndecan-2 and downstream beta1-integrin-mediated adhesion and cytoskeletal organization, requiring Src kinase and PI3K C2beta isoform. |
Co-immunoprecipitation, domain mapping using truncation mutants, cell adhesion assays with CD148 blocking, Src inhibitor and PI3K inhibitor experiments |
Molecular biology of the cell |
Medium |
21813734
|
| 2012 |
Thrombospondin-1 (TSP1) is an extracellular ligand for CD148: soluble TSP1 binds CD148 ectodomain with high affinity, increases CD148 catalytic activity, and mediates TSP1-dependent inhibition of cell growth through CD148; soluble CD148 ectodomain or CD148 gene silencing antagonizes TSP1-mediated growth inhibition. |
Biotin surface labeling and affinity purification of CD148-interacting proteins, mass spectrometry identification, binding affinity assays, CD148 transfection in CD148-negative cells, CD148 siRNA knockdown, growth inhibition assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
22308318
|
| 2012 |
DEP-1 is phosphorylated on Y1311 and Y1320 in a Src- and Fyn-dependent manner; these phosphotyrosines bind the Src SH2 domain, allowing DEP-1 to dephosphorylate Src inhibitory Y529 and promote activation of Src substrates VE-cadherin and Cortactin. RNAi knockdown or DEP-1 Y1311F/Y1320F expression impairs VEGF-induced Src-dependent permeability, invasion, and capillary formation. At high DEP-1 expression (confluent cells), DEP-1 also dephosphorylates Src Y418, attenuating downstream signaling. |
Phospho-site mutagenesis (Y1311F, Y1320F), co-immunoprecipitation, in vitro phosphorylation/dephosphorylation assays, siRNA knockdown, permeability and invasion assays |
Blood |
High |
22898603
|
| 2013 |
The large ectodomains of CD148 and CD45 mediate their passive, size-based exclusion from ligated TCR at the immunological synapse; truncating the ectodomain of CD148 enhanced its co-localization with ligated TCR and increased its inhibitory effect on TCR signaling, supporting a kinetic-segregation model. |
Expression of WT vs. truncated ectodomain CD148 and CD45 in T cells, NFAT reporter assay, confocal imaging at immunological synapse |
Blood |
Medium |
23580664
|
| 2011 |
In neutrophils, CD148 positively and negatively regulates GPCR-mediated chemoattractant signaling (Ca2+, PI3K, pERK) and preferentially targets the Src family kinase Lyn (versus CD45, which targets Hck and Fgr), revealing distinct SFK substrate preferences between CD45 and CD148 in GPCR pathways. |
CD148 and CD45 single and double knockout mice, neutrophil chemotaxis and Ca2+ flux assays, phospho-SFK immunoblotting, S. aureus infection model |
Immunity |
High |
22078799
|
| 2013 |
CD148 promotes airway hyperresponsiveness (AHR) through positive regulation of Src family kinases in airway smooth muscle (ASM): CD148-deficient mice are protected from AHR in two asthma models; CD148 deficiency in smooth muscle reduces the frequency of calcium oscillations and causes hyperphosphorylation of SFK inhibitory C-terminal tyrosine in ASM, identifying CD148 as a critical SFK activator in ASM contractility. |
Ptprj whole-body and smooth-muscle-specific conditional knockout mice, two allergen-challenge asthma models, methacholine challenge for AHR, SFK phospho-immunoblotting, ASM calcium imaging |
The Journal of clinical investigation |
High |
23543053
|
| 2014 |
CK2 phosphorylates DEP-1 on T1318, a residue proximal to Y1320; T1318 phosphorylation promotes Y1320 phosphorylation and Src SH2-domain recruitment to DEP-1, thereby enabling DEP-1-catalyzed Src Y529 dephosphorylation and VEGF-induced endothelial cell permeability. A T1318A mutant reduces Y1320 phosphorylation, Src association, and permeability, while the phosphomimetic T1318E enhances them. |
Site-directed mutagenesis (T1318A, T1318E), phospho-specific immunoblotting, co-immunoprecipitation, in vitro CK2 kinase assay, CK2 siRNA knockdown, permeability assay |
Cellular signalling |
High |
24583284
|
| 2016 |
DEP-1-deficient mice show abrogated VEGF-induced vascular leakage and impaired Src activation and VE-cadherin phosphorylation in vivo; angiogenesis in Matrigel plug and aortic ring assays is defective in the absence of DEP-1; tumor growth-associated angiogenesis and experimental lung metastasis are markedly reduced in DEP-1 KO mice, establishing DEP-1 as an essential in vivo driver of VEGF-dependent permeability, angiogenesis, and metastasis via Src activation. |
DEP-1 knockout mice, systemic VEGF injection with vascular leakage measurement (Miles assay), Matrigel plug and aortic ring angiogenesis assays, tumor implantation and metastasis models, phospho-Src and phospho-VE-cadherin immunoblotting |
Cancer research |
High |
27364551
|
| 2016 |
DEP-1-deficient mouse retinas show increased tip cell number and vessel branching, increased ERK1/2 phosphorylation, and decreased Dll4 expression and Notch activation; mechanistically, DEP-1 promotes VEGF-induced Dll4 expression through a Src/Akt/beta-catenin signaling pathway, and DEP-1 mutants unable to activate Src do not rescue Dll4 expression, placing DEP-1 upstream of the Dll4-Notch pathway in sprouting angiogenesis. |
DEP-1 KO mice (retinal vascular analysis), DEP-1 siRNA in HUVECs, overexpression of WT and Src-activation-defective DEP-1 mutants, Src/Akt/beta-catenin inhibitor experiments, phospho-histone H3 staining |
Angiogenesis |
High |
31598898
|
| 2017 |
PTPRJ dephosphorylates JAK2 at Y813 and Y868 autophosphorylation sites, thereby negatively regulating leptin receptor–JAK2 signaling in hypothalamic neurons; Ptprj-deficient mice show enhanced leptin signaling and reduced weight gain, and diet-induced obesity upregulates PTPRJ expression in the hypothalamus causing leptin resistance. |
Ptprj knockout mice, overexpression in hypothalamic neurons, in vitro dephosphorylation assay with site-specific mutants, JAK2 phosphorylation immunoblotting, food intake and body weight measurements |
Scientific reports |
High |
28912580
|
| 2015 |
DEP-1 is required for insulin signaling: Ptprj knockout mice on high-fat diet show enhanced insulin sensitivity and improved glucose tolerance; DEP-1 deficiency increases phosphorylation of insulin signaling cascade components (liver, muscle, adipose tissue) after insulin challenge, and DEP-1 downregulation in skeletal muscle cells increases glucose uptake, identifying DEP-1 as a negative regulator of insulin signaling. |
Ptprj conventional knockout mice, high-fat diet, metabolic phenotyping (glucose/insulin tolerance tests), phospho-insulin signaling immunoblotting in tissues, glucose uptake assay in skeletal muscle cells with DEP-1 siRNA |
Molecular metabolism |
Medium |
25830095
|
| 2018 |
PTPRJ is required for megakaryocyte maturation and platelet biogenesis: biallelic loss-of-function PTPRJ variants in patients cause inherited thrombocytopenia with small platelets and impaired platelet responses to GPVI agonists; the mechanism involves reduced activation of Src family kinases. CRISPR/Cas9 ablation of ptprja in zebrafish reduced CD41+ thrombocytes in vivo. Silencing PTPRJ in human megakaryocytic cell line reproduced defects in SDF1-driven migration and proplatelet formation. |
Exome sequencing of patients, CRISPR/Cas9 zebrafish model, patient megakaryocyte functional assays (migration, proplatelet formation), PTPRJ siRNA in megakaryocytic cell line, phospho-SFK immunoblotting, platelet aggregation assays |
Blood |
High |
30591527
|
| 2018 |
PTPRJ negatively modulates CD98hc protein levels in A549 lung cancer cells; PTPRJ overexpression reduces CD98hc protein abundance, and co-treatment with the proteasome inhibitor MG132 prevents the decrease, indicating that PTPRJ promotes CD98hc proteasomal degradation; PTPRJ–CD98hc interaction was validated by co-immunoprecipitation. |
Proteomic pulldown to identify PTPRJ-interacting proteins, co-immunoprecipitation, overexpression with and without proteasome inhibitor MG132, cell proliferation and apoptosis assays |
Oncotarget |
Medium |
29805737
|
| 2018 |
PTPRJ regulates retinal axon projections by dephosphorylating EphA/EphB receptors and c-Abl kinase: Ptprj KO mice show enhanced Eph receptor phosphorylation in retinas, increased ipsilateral retinal axon projections, and anteriorly shifted ectopic terminal zones in the superior colliculus; c-Abl was identified as a novel PTPRJ substrate, with elevated c-Abl phosphorylation in Ptprj KO retinas. |
Ptprj knockout mice and Ptpro/Ptprj double knockout mice, retinal axon tracing, phospho-Eph and phospho-c-Abl immunoblotting, substrate identification in cultured mammalian cells |
The Journal of neuroscience |
Medium |
30082414
|
| 2017 |
In C. elegans, DEP-1 dephosphorylates Y792 in the membrane-proximal NPXY motif of the beta-integrin subunit PAT-3, promoting integrin activation via talin recruitment; non-phosphorylatable pat-3(Y792F) partially suppresses the hyperactive EGFR signaling caused by dep-1 loss; FRAP analysis shows that the integrin/talin complex restricts EGFR mobility on the basolateral membrane, revealing a mechanism by which DEP-1 attenuates EGFR signaling partly through integrin activation in addition to direct EGFR dephosphorylation. |
Substrate-trapping DEP-1 mutant with proteomics, genetic epistasis (dep-1 loss-of-function + pat-3 phospho-mutant), in vivo FRAP analysis of EGFR mobility |
PLoS genetics |
High |
28135265
|
| 1997 |
DEP-1 is constitutively associated with a 64-kDa serine/threonine kinase in multiple tumor cell lines; this kinase forms a stable complex with DEP-1 and phosphorylates DEP-1 and DEP-1-interacting proteins in vitro, suggesting regulation of DEP-1 by serine/threonine phosphorylation. |
Co-immunoprecipitation, in vitro kinase assay with GST-DEP-1-C/S fusion, immunoblotting for serine/threonine phosphorylation |
The Journal of biological chemistry |
Low |
9115287
|
| 2010 |
CD148 maintains a pool of active Src family kinases in platelets by directly dephosphorylating the inhibitory C-terminal tyrosines of Fyn, Lyn, and Src in vitro; this is essential for GPVI-FcR gamma-chain expression and collagen-mediated platelet activation. CD148 also paradoxically dephosphorylates the SFK activation loop in vitro. |
CD148 KO mouse platelets, DT40/NFAT-luciferase reporter system, biochemical in vitro dephosphorylation assay with recombinant CD148, phospho-specific immunoblotting |
Journal of thrombosis and haemostasis |
High |
20345711
|
| 2011 |
CD148 dephosphorylates the C-terminal inhibitory tyrosine of Src family kinases (SFKs) involved in TCR signaling; although CD148 has both activating and inhibitory effects on TCR SFKs, in the absence of CD45, CD148 activating effects prevail and functionally complement CD45 deficiency in human T cell lines. This complementation is independent of the tyrosines in the CD148 C-terminal tail, arguing against the phosphotyrosine displacement model as the sole activation mechanism. |
CD148-deficient and CD45/CD148-deficient primary murine B cells, T cell lines; phospho-SFK immunoblotting; T cell functional assays; CD148 C-terminal tail tyrosine mutants in human T cell lines |
The Journal of biological chemistry |
Medium |
21543337
|
| 2016 |
CD148 positively regulates Lyn kinase selectively in B1 but not B2 B cells: CD148 loss-of-function causes defective B1 B cell antigen receptor signaling downstream of Lyn, impaired TI antibody responses, and altered B1 BCR repertoire selection, while B2 cell signaling is intact. |
CD148 conditional knockout mice, B1 vs. B2 B cell functional assays, BCR signaling phospho-immunoblotting, NP-ficoll and Pneumovax 23 immunization |
Immunity |
High |
27889108
|
| 2021 |
CD148 deficiency in fibroblasts promotes pulmonary fibrosis: fibroblast-specific CD148 KO mice exhibit increased bleomycin-induced fibrosis; mechanistically, CD148-deficient fibroblasts show hyperactivated PI3K/Akt/mTOR signaling, reduced autophagy, and p62 accumulation, which activates NF-κB and drives profibrotic gene expression. A syndecan-2-derived CD148-activating peptide (SDC2-pep) reduces fibrosis in vivo. |
Conditional fibroblast-specific CD148 KO mice (bleomycin model), CD148 siRNA and overexpression in IPF fibroblasts, PI3K/Akt/mTOR phospho-immunoblotting, autophagy and p62 assays, NF-κB reporter, precision-cut lung slices from IPF patients |
American journal of respiratory and critical care medicine |
High |
33784491
|
| 2016 |
DEP-1 promotes microglial migration and phagocytosis in part by inhibiting the Src family kinase Fyn: DEP-1 depletion in BV2 cells enhances pFyn Y420 and Fyn kinase activity, and DEP-1 loss or Fyn knockout in mice produces opposite effects on microglial function (DEP-1 KO reduces migration; Fyn KO increases migration), consistent with DEP-1 activating migration by suppressing Fyn. |
DEP-1 shRNA knockdown in BV2 cells, Ptprj−/− and Fyn−/− mice, in vitro migration/phagocytosis assays, in vivo wounding assay, Fyn immunoprecipitation kinase assay |
Glia |
Medium |
27859601
|
| 2011 |
Syndecan-4 inhibits T cell activation by recruiting CD148 through syntenin as a bridging molecule; binding of DC-HIL to SD-4 assembles the SD-4/syntenin/CD148 complex and upregulates CD148 PTP activity, which mediates the inhibitory function of SD-4 in T cells. |
Co-immunoprecipitation of SD-4/syntenin/CD148 complex, PTP activity assay after DC-HIL ligation, T cell activation assays with CD148 inhibition |
European journal of immunology |
Medium |
21469128
|
| 2008 |
In zebrafish, Dep1 (ortholog of mammalian PTPRJ) acts upstream of PI3K in arterial/venous cell fate specification: Dep1a/Dep1b morpholino knockdown causes defective circulation and reduced arterial markers with expanded venous markers; the arterial specification defect is rescued by PI3K inhibition and by active Notch/Grl expression, placing Dep1 upstream of PI3K in a pathway leading to Notch/Grl-dependent arterial identity. |
Morpholino knockdown of Dep1a and Dep1b in zebrafish, arterial/venous marker analysis, PI3K inhibitor rescue, active Notch/Grl rescue |
Developmental biology |
Medium |
18835554
|
| 2020 |
PTPRJ (CD148) and Csk are co-essential regulators of platelet SFK activity: Csk/CD148 double-deficient mice show dramatic increases in SFK activity but paradoxically reduced thrombosis due to negative feedback (upregulation of Chk, ITIM receptor G6b-B, Shp1/Shp2); deletion of PTPRJ in Chk/Csk double KO mice partially rescues thrombocytopenia and reduces inhibitory phosphorylation of Src and Fyn, revealing PTPRJ as the primary activating counterpart to Csk in maintaining platelet SFK balance. |
Triple KO mice (Chk, Csk, Ptprj in MK lineage), analog-sensitive Csk mouse, phospho-SFK immunoblotting, platelet count and aggregation assays, G6b-B/Shp1/Shp2 interaction assays |
Blood |
High |
32016283
|