Affinage

SIRPA

Tyrosine-protein phosphatase non-receptor type substrate 1 · UniProt P78324

Length
504 aa
Mass
55.0 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SIRPA is an inhibitory immunoreceptor on myeloid cells that functions as the principal receptor for CD47, transducing a 'don't eat me' signal that restrains phagocytosis, cytokine production, and integrin-mediated cell activation. CD47 engagement repositions SIRPA to the phagocytic synapse where its cytoplasmic ITIM tyrosines—phosphorylated by Src-family kinases, FAK, or JAK2 downstream of integrins, growth factors, or TLRs—recruit SHP-1 and SHP-2 phosphatases that inhibit inside-out integrin activation, suppress NF-κB-dependent inflammatory cytokine release, and modulate Rho/Rac-dependent cytoskeletal reorganization and cell migration (PMID:32768386, PMID:18233962, PMID:9582366, PMID:11118207). Beyond phagocytosis inhibition, SIRPA scaffolds adhesion-regulated signaling complexes containing SKAP55hom/R, FYB/SLAP-130, and PYK2, and channels growth-factor signals through SHP-2 to MAP kinase, PI3K/Akt, and PDK1 pathways that regulate cell survival and proliferation (PMID:10469599, PMID:9535915, PMID:20643654). SIRPA also operates in non-immune contexts: it localizes to neuronal synapses in a CD47-dependent manner, marks committed cardiomyocytes derived from human pluripotent stem cells, and mediates CD47-dependent osteoclast fusion (PMID:10602092, PMID:22020386, PMID:21638321).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1998 High

    Establishing how SIRPA becomes phosphorylated: cell adhesion to extracellular matrix and growth-factor stimulation (insulin, GH) each trigger SIRPA ITIM tyrosine phosphorylation via Src/FAK or JAK2, recruiting SHP-2 to specific phosphotyrosines, revealing SIRPA as a convergent signaling scaffold for multiple upstream stimuli.

    Evidence In vitro kinase assays, FAK-deficient cells, co-IP, site-directed mutagenesis with SPR in CHO cells and COS cells

    PMID:9507023 PMID:9535915 PMID:9582366

    Open questions at the time
    • Direct kinase-substrate relationship for SIRPA phosphorylation in intact cells not reconstituted
    • Relative contributions of individual tyrosines to distinct downstream pathways not fully resolved
  2. 1999 High

    Identifying CD47 as the physiological ligand of SIRPA resolved the key question of what extracellular signal controls this receptor, while parallel work showed SIRPA scaffolds multi-protein adhesion complexes independent of its own phosphorylation state.

    Evidence Expression cloning, co-IP, immunohistochemistry for CD47-SIRPA binding; mass spectrometry and co-IP identifying SKAP55hom/R, FYB/SLAP-130, PYK2 complexes in macrophages

    PMID:10469599 PMID:9872987

    Open questions at the time
    • Stoichiometry and dynamics of multi-protein complex assembly on SIRPA unknown
    • Whether scaffold function and ITIM signaling operate simultaneously or sequentially not determined
  3. 2000 High

    Genetic deletion of the SIRPA cytoplasmic domain established its requirement for Rho activation, polarized cell migration, and proper synaptic localization of SIRPA in neurons, extending SIRPA's role beyond immune cells.

    Evidence Knock-in mouse fibroblasts with cytoplasmic-deletion mutant; Rho/Rac activation assays, migration assays; IAP-null mouse retina ultrastructural analysis

    PMID:10602092 PMID:11118207

    Open questions at the time
    • Molecular link between SIRPA cytoplasmic domain and Rho GEF/GAP regulation unidentified
    • Neuronal functional consequences of SIRPA synaptic mislocalization not tested
  4. 2002 High

    In vivo phenotyping of SIRPA cytoplasmic-mutant mice revealed that SIRPA negatively regulates macrophage phagocytosis and is required for normal platelet survival, providing the first genetic evidence for SIRPA as the key 'don't eat me' effector.

    Evidence Knock-in mutant mice with accelerated platelet clearance, enhanced macrophage phagocytosis ex vivo

    PMID:12167615

    Open questions at the time
    • Whether SHP-1 vs SHP-2 mediates the dominant anti-phagocytic signal not separated
    • Contribution of soluble vs membrane-bound SIRPA to platelet clearance not addressed
  5. 2003 Medium

    Multiple studies revealed post-translational regulation of SIRPA itself: the cytoplasmic region controls ectodomain affinity for CD47 and cis-dimerization, while immature SIRPA is a substrate of SCF(NFB42) E3 ligase-mediated ERAD, adding layers of regulation beyond ligand binding.

    Evidence Cytoplasmic deletion/4F mutant binding and crosslinking assays; ubiquitination assay with NFB42 identification and surface SIRPA flow cytometry

    PMID:12963030 PMID:14701835

    Open questions at the time
    • Structural basis for cytoplasmic domain control of ectodomain conformation unresolved
    • Physiological conditions triggering ERAD-mediated SIRPA degradation not defined
    • NFB42-SIRPA relationship confirmed only by single lab
  6. 2004 High

    Metalloproteinase-mediated ectodomain shedding of SIRPA was shown to regulate cell migration and focal adhesion signaling, while aberrant N-glycosylation in melanoma cells was found to uncouple SIRPA from CD47 binding, revealing tumor escape from CD47-mediated migration inhibition.

    Evidence In vitro cleavage assay with shedding-resistant mutant; glycosylation inhibitor treatment of B16 melanoma; CD47-Fc binding and migration assays

    PMID:14739297 PMID:15123722

    Open questions at the time
    • Identity of the specific metalloproteinase(s) mediating SIRPA shedding not determined
    • In vivo significance of soluble SIRPA ectodomain not established at this time
  7. 2007 High

    Crystal structure of SIRPA's IgV domain revealed CDR-like loops mediating CD47 recognition, and genetic studies showed that polymorphic variation in these loops (NOD vs other strains) determines CD47 binding affinity and macrophage phagocytosis efficiency, explaining strain-dependent xenotransplantation outcomes.

    Evidence X-ray crystallography with mutagenesis; site-directed mutagenesis reconstituting CD47 binding in SIRPβ; positional genetics and binding assays in NOD xenotransplantation

    PMID:17982459 PMID:18025220 PMID:18045614

    Open questions at the time
    • Co-crystal structure of SIRPA–CD47 complex not yet available at this time
    • Whether polymorphic variation affects signaling strength or only binding affinity not tested
  8. 2008 High

    SIRPA's role was extended to innate immune regulation: TLR stimulation phosphorylates SIRPA via Src kinases, and SIRPA ITIMs suppress NF-κB-dependent TNFα and IL-6 production; separately, surfactant proteins SP-A/SP-D were identified as additional SIRPA ligands that suppress alveolar macrophage efferocytosis via SHP-1/RhoA.

    Evidence 4F and deltaCyto mutants in RAW264.7 macrophages with NF-κB assays; blocking antibodies and SHP-1 KO mice in alveolar macrophage phagocytosis; SIRPA-transfected fibroblasts

    PMID:18233962 PMID:18420961

    Open questions at the time
    • Relative contribution of SHP-1 versus SHP-2 to TLR-stimulated NF-κB inhibition not dissected
    • Whether SP-A/SP-D and CD47 compete for the same SIRPA binding site not determined
  9. 2011 High

    SIRPA was identified as a specific surface marker of human pluripotent stem cell-derived cardiomyocytes and shown to regulate osteoclast fusion via SHP-1-mediated dephosphorylation of non-muscle myosin IIA, broadening its non-immune roles.

    Evidence Systematic 370-antibody screen with FACS and troponin T validation; CD47-KO bone marrow osteoclast assays with histomorphometry

    PMID:21638321 PMID:22020386

    Open questions at the time
    • Functional role of SIRPA in cardiomyocyte biology beyond marker utility unknown
    • Whether myosin IIA is a direct SHP-1 substrate or indirect target not confirmed
  10. 2020 High

    A reconstituted phagocytic system demonstrated that CD47 repositions SIRPA to the phagocytic synapse where it specifically inhibits inside-out integrin activation, and chemical bypass of integrin inhibition rescues engulfment, establishing integrin suppression as the core effector mechanism of the 'don't eat me' signal.

    Evidence Reconstituted phagocytic system with defined signals, live imaging, chemical integrin activators, blocking antibodies

    PMID:32768386

    Open questions at the time
    • Specific phosphatase target on integrin signaling cascade (talin, kindlin, or other) not identified
    • Whether this integrin-centric mechanism applies equally in dendritic cells and neutrophils not tested
  11. 2023 Medium

    Tumor-cell-intrinsic SIRPA was found to activate ERK–SP1–SLC7A3 signaling in osteosarcoma, driving arginine uptake and metastasis, revealing a cell-autonomous oncogenic signaling role for SIRPA independent of its immune-inhibitory function.

    Evidence Knockdown/overexpression, phosphorylation analysis, ChIP, proteasome inhibition, in vivo xenograft metastasis

    PMID:37769797

    Open questions at the time
    • How SIRPA activates ERK in tumor cells without known ligand engagement not explained
    • Generalizability beyond osteosarcoma not established
    • Single-lab finding awaiting independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the direct SHP-1/SHP-2 substrate that mediates integrin inhibition at the phagocytic synapse, how the SIRPA cytoplasmic domain allosterically controls ectodomain binding affinity and dimerization, and whether tumor-intrinsic SIRPA signaling represents a general oncogenic mechanism or is context-specific.
  • Direct phosphatase substrate at the phagocytic synapse unidentified
  • Structural basis for cytoplasmic-to-ectodomain allosteric communication unknown
  • Tumor-intrinsic SIRPA signaling pathway not independently replicated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 4
Partners
CD47GRB2JAK2PDK1PYK2SHP1SHP2SKAP1

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 SIRPA (P84/SHPS-1) was identified as a binding partner of CD47 (integrin-associated protein/IAP) via expression cloning, establishing CD47 as the predominant ligand of SIRPA with virtually identical tissue distribution in the brain. Expression cloning, co-immunoprecipitation, immunohistochemistry The Journal of biological chemistry High 9872987
1998 Cell adhesion to extracellular matrix proteins (fibronectin, laminin) induces tyrosine phosphorylation of SHPS-1/SIRPA and its association with SHP-2, requiring both focal adhesion kinase (FAK) and Src family kinases (Src/Fyn) but not FAK as a direct kinase of SHPS-1 cytoplasmic domain in vitro. In vitro kinase assay, overexpression of Csk, FAK-deficient cells, co-immunoprecipitation The Journal of biological chemistry High 9582366
1998 Insulin induces tyrosine phosphorylation of SHPS-1/SIRPA at Tyr449 and Tyr473; SHP-2 binds to these phosphotyrosines via its N-terminal and C-terminal SH2 domains respectively, and SHPS-1 overexpression enhances insulin-induced MAP kinase activation dependent on these sites. Site-directed mutagenesis, surface plasmon resonance, in vitro phosphatase assay, overexpression in CHO cells The Journal of biological chemistry High 9535915
1998 Growth hormone (GH) stimulates tyrosine phosphorylation of SIRPalpha and enhances its association with SHP-2 via JAK2; co-expression of SIRPalpha and JAK2 results in SIRPalpha tyrosyl phosphorylation and JAK2 association with SIRPalpha. Co-immunoprecipitation, COS cell co-expression, immunoprecipitation-kinase assay The Journal of biological chemistry Medium 9507023
1999 SHPS-1/SIRPA serves as a scaffold assembling two distinct adhesion-regulated multi-protein complexes in macrophages: one containing SKAP55hom/R and FYB/SLAP-130, and another containing PYK2; FYB/SLAP-130 recruitment required SKAP55hom/R, whereas PYK2 associated independently, and complex formation was independent of SHP-1 and SHPS-1 tyrosine phosphorylation. Mass spectrometry, co-immunoprecipitation, integrin-mediated adhesion assays Current biology : CB High 10469599
2000 Fibroblasts expressing SHPS-1 mutant lacking the cytoplasmic region showed increased actin stress fibers and focal adhesions, spread faster on fibronectin but were defective in polarized migration, and had markedly reduced adhesion-induced Rho (but not Rac) activation, establishing SHPS-1/SIRPA's role in integrin-mediated cytoskeletal reorganization and cell motility via Rho regulation. Knock-in mouse fibroblasts with cytoplasmic-deletion mutant, phalloidin staining, Rho/Rac activation assays, migration assays The EMBO journal High 11118207
2002 Mice homozygous for SHPS-1/SIRPA cytoplasmic-deletion mutation exhibit thrombocytopenia due to accelerated platelet clearance; peritoneal macrophages from mutant mice showed enhanced phagocytosis of red blood cells and increased cell spreading, establishing SIRPA's role in negative regulation of macrophage phagocytic response and platelet survival. Knock-in mutant mice, platelet clearance assays, ex vivo macrophage phagocytosis assays The Journal of biological chemistry High 12167615
2002 IGF-I stimulates SHPS-1/SIRPA phosphorylation which recruits SHP-2 to the plasma membrane; SHP-2 is then recruited to IGF-IR and mediates receptor dephosphorylation; cells expressing SHPS-1 mutant unable to bind SHP-2 show no SHP-2 recruitment to IGF-IR and prolonged IGF-IR phosphorylation. Mutant SHPS-1 expression, co-immunoprecipitation, phosphorylation kinetics assays in smooth muscle cells The Journal of biological chemistry Medium 11779860
2003 Ligation of MyD-1/SIRPA on monocytes recruits SHP-2 and sequentially activates PI3-kinase, phospholipase D, and sphingosine kinase; this pathway selectively inhibits LPS-induced TNFα secretion, as wortmannin (PI3K inhibitor) restores normal TNFα production. Inhibitor studies (wortmannin), signaling pathway assays, cytokine measurement in PBMCs Blood Medium 12805067
2004 Ectodomain shedding of SHPS-1/SIRPA is mediated by a metalloproteinase at the juxtamembrane region, promoted by PKC or Ras activation, releases minimal CD47-binding activity; an SHPS-1 shedding-resistant mutant impairs cell migration, spreading, actin reorganization, and increases paxillin and FAK tyrosine phosphorylation. In vitro metalloproteinase cleavage assay, mutant SHPS-1 expression, cell migration and spreading assays, phosphorylation analysis The Journal of biological chemistry High 15123722
2004 CD47 binding to SHPS-1/SIRPA on non-tumorigenic melanocytes inhibits cell migration; B16 melanoma cells resist this inhibition due to aberrant N-glycosylation of SHPS-1 that prevents CD47 binding; CD47 binding induces proteasome-mediated degradation of SHPS-1 and reduces tyrosine phosphorylation of focal adhesion kinase. CD47-Fc binding assay, glycosylation inhibitor (1-deoxymannojirimycin), cell migration assays, proteasome inhibition The Journal of biological chemistry Medium 14739297
2004 SIRPgamma, a third SIRP family member expressed on T and B cells (not myeloid cells), binds CD47 with lower affinity (Kd ~23 µM) compared with SIRPalpha (Kd ~2 µM); its short cytoplasmic tail lacks signaling motifs and does not interact with DAP12, suggesting unidirectional CD47 signaling only. Soluble protein binding assay (affinity measurements), mAb characterization, DAP12 co-expression studies Journal of immunology Medium 15294972
2007 NOD SIRPA shows enhanced binding to human CD47 compared with other mouse strains; NOD SIRPA expression on macrophages is required for support of human hematopoiesis in xenotransplantation, establishing SIRPA-CD47 binding as the mechanistic determinant of engraftment efficiency. Positional genetics, binding assays, macrophage-specific functional assays in xenotransplantation model Nature immunology High 17982459
2007 Crystal structure of murine SHPS-1/SIRPA ligand-binding domain reveals an I2-set Ig fold resembling IgV antigen receptor domains; site-directed mutagenesis identified critical residues for CD47 binding in the C'E loop and CDR-like regions; these variable loop structures mediate CD47 recognition analogous to antigen receptor mechanisms. X-ray crystallography, site-directed mutagenesis, CD47 binding assays Journal of molecular biology High 18045614
2007 Site-directed mutagenesis identified three residues in the D1 domain of SIRPalpha critical for CD47 binding; N-glycosylation is not required for binding; cumulative substitution of critical residues into SIRPbeta conferred de novo CD47 binding, and two distinct but adjacent regions on the membrane-distal Ig loop are required. Site-directed mutagenesis, de novo binding reconstitution in SIRPbeta, epitope mapping with anti-SIRP antibodies, homology modeling Journal of immunology High 18025220
2008 Surfactant proteins SP-A and SP-D suppress alveolar macrophage phagocytosis of apoptotic cells by directly binding SIRPA; blockade of SIRPA, or inhibition of downstream SHP-1 and RhoA, reverses this suppression; transfected fibroblasts with active vs mutant SIRPA confirmed binding dependence. Blocking antibodies, SIRPA-transfected fibroblasts with active/mutant forms, SHP-1 KO mice, pharmacological inhibitors, phagocytosis assays American journal of respiratory and critical care medicine High 18420961
2008 Mice expressing SHPS-1/SIRPA with mutated cytoplasmic region (4F mutant) are resistant to collagen-induced arthritis; mutant mice show reduced CII-specific IgG/IgG2a, IL-1β, and decreased T cell proliferation/cytokine production, establishing SHPS-1 cytoplasmic signaling as essential for CIA development. Knock-in mutant mice, arthritis model (CIA), serum cytokine/antibody measurement, T cell proliferation assays Biochemical and biophysical research communications Medium 18455510
2008 LPS or poly(I:C) induces tyrosine phosphorylation of SHPS-1/SIRPA via a Src family kinase and subsequent association with SHP-1 and SHP-2; SHPS-1 negatively regulates TLR4/TLR3-dependent TNFα and IL-6 production through inhibition of NF-κB signaling, as shown by the 4F mutant markedly promoting cytokine production. Mutant SHPS-1 expression (4F and deltaCyto), NF-κB activation assay, cytokine measurement in RAW264.7 macrophages Genes to cells Medium 18233962
2009 SIRPA selectively marks CD11b(high)CD103(-) airway dendritic cells; CD47 expression on DCs governs SIRPA+ DC migration to mediastinal lymph nodes; CD47-/- DCs fail to elicit TH2 responses and adoptive transfer of CD47+/+ but not CD47-/- SIRPA+ DCs restores TH2 responses, establishing CD47-SIRPA interaction as controlling DC trafficking and allergic inflammation. CD47 knockout mice, DC adoptive transfer, SIRPA-Fc fusion molecule administration, allergic asthma models The Journal of allergy and clinical immunology High 19748659
2010 PDK1 is recruited to the SHPS-1/SIRPA signaling complex following IGF-I stimulation via Grb2 (which binds Pyk2 on SHPS-1); PDK1's proline-rich sequence binds Grb2 SH3 domain; recruited PDK1 is further activated by Tyr373/376 phosphorylation, required for AKT Thr308 phosphorylation and IGF-I-mediated cell survival. Co-immunoprecipitation, dominant-negative and mutant expression, kinase activity assays, apoptosis assays in smooth muscle cells The Journal of biological chemistry Medium 20643654
2011 SIRPA is specifically expressed on cardiomyocytes derived from human pluripotent stem cells; antibody-based cell sorting with anti-SIRPA yields up to 98% cardiac troponin T-positive cells, demonstrating SIRPA as a definitive cell-surface marker identifying committed cardiomyocytes. CD antibody panel screen (370 antibodies), FACS sorting, cardiac troponin T immunostaining, contractility assessment Nature biotechnology High 22020386
2011 Disruption of the CD47-SHPS-1/SIRPA association impairs osteoclastogenesis at the point of fusion (not differentiation), associated with lack of SHPS-1 phosphorylation, failure of SHP-1 recruitment, and absence of non-muscle myosin IIA dephosphorylation; CD47-/- mice show skeletal defects with impaired osteoblast and osteoclast function. CD47 knockout mice, bone marrow osteoclast differentiation assays, histomorphometry, phosphorylation analysis Journal of bone and mineral research Medium 21638321
2013 NOD-specific polymorphic SIRPA is the sole genetic determinant for efficient human cell engraftment in NOD-based xenotransplantation models; introduction of NOD-Sirpa into non-NOD C57BL/6.Rag2nullIl2rgnull background confers engraftment efficiency equal to or exceeding NOD-based strains. Congenic mouse generation (BRGS line), human hematopoietic engraftment assays, positional genetics Blood High 23293079
2013 BALB/c-specific L29V SNP within the IgV domain of SIRPA increases its affinity for human CD47 compared to C57BL/6 SIRPA, conferring intermediate phagocytosis inhibition against human HSCs and intermediate xenotransplantation efficiency. Binding affinity assays, macrophage phagocytosis assays, long-term culture-initiating cell assays Experimental hematology Medium 24269920
2017 Treg cells protect dopaminergic neurons against MPP+ neurotoxicity through direct cell-to-cell contact via CD47 (on Treg) binding to SIRPA (on neurons); this interaction activates Rac1/Akt signaling in neurons; silencing CD47 in Tregs or SIRPA in neurons abrogates neuroprotection. Live cell imaging, siRNA knockdown, transwell co-culture, Rac1/Akt pathway inhibition, TH+ neuron counting Cellular physiology and biochemistry Medium 28268219
2020 CD47 ligation repositions SIRPA to the phagocytic synapse where it inhibits inside-out integrin activation, limiting macrophage spreading across engulfment targets; chemical reactivation of integrin bypasses CD47-SIRPA inhibition and rescues engulfment, placing SIRPA-mediated integrin inhibition as the mechanistic basis for the 'don't eat me' signal. Reconstituted phagocytic system with defined signals, live imaging, chemical integrin activators, blocking antibodies Immunity High 32768386
2022 Soluble SIRPA promotes acute lung injury by suppressing macrophage phagocytosis through activation of SHP-1, which subsequently inhibits downstream STAT3 and STAT6 signaling; SIRPA knockout mice show attenuated ALI with improved phagocytosis and STAT3/STAT6 activation. SIRPA knockout mice, LPS-induced ALI model, pharmacological SHP-1 inhibition (TPI-1), STAT3/STAT6 inhibitors, macrophage phagocytosis assays Frontiers in immunology Medium 35634325
2023 Tumor-cell-intrinsic SIRPA activates ERK to phosphorylate SP1 at Thr278, protecting SP1 from proteasomal degradation; stabilized SP1 drives SLC7A3 expression, increasing arginine uptake which in turn further stabilizes SP1 (forming a 'SP1 stabilization circle'), promoting osteosarcoma cell migration and metastasis. Knockdown/overexpression, phosphorylation analysis, proteasome inhibition, ChIP (SP1-SLC7A3 promoter), in vivo xenograft metastasis model Cancer letters Medium 37769797
2022 MiR-382 promotes M2-like macrophage polarization in renal fibrosis by directly targeting and suppressing SIRPA expression (validated by dual-luciferase assay); SIRPA knockdown upregulates phosphorylated STAT3 (S727 and Y705), and STAT3 inhibition attenuates M2 polarization and kidney fibrosis. miR-382 KO mice, dual-luciferase reporter assay, adoptive macrophage transfer, STAT3 inhibition, flow cytometry Frontiers in immunology Medium 35585990
2003 The cytoplasmic region of SHPS-1/SIRPA regulates its binding affinity for CD47, cis-dimerization, and actin cytoskeletal reorganization; loss of the cytoplasmic region increases CD47 binding affinity and SHPS-1 oligomerization, while wild-type SHPS-1 promotes lamellipodium formation at migrating cell leading edges. Cytoplasmic deletion and 4F mutant CHO cell expression, CD47-Fc binding assay, chemical crosslinking, actin staining Biochemical and biophysical research communications Medium 12963030
2003 Immature SHPS-1/SIRPA is a physiological substrate for the SCF(NFB42) E3 ubiquitin ligase, which mediates its polyubiquitination and proteasomal degradation during ER stress; NFB42 expression suppresses aggresome formation, increases mature SHPS-1 at the cell surface, and reduces eIF2alpha phosphorylation. Co-immunoprecipitation, ubiquitination assay, NFB42 expression/mutant studies, flow cytometry of surface SHPS-1 The Journal of biological chemistry Medium 14701835
2000 P84/SHPS-1/SIRPA is expressed at synaptic sites in mouse retina; IAP/CD47 expression precedes P84 at synapses, and in IAP-null retinae P84 fails to localize to synaptic sites, demonstrating that CD47-SIRPA interaction is required for SIRPA synaptic localization. Immunohistochemistry, electron microscopy, IAP-null transgenic mouse retina analysis The Journal of comparative neurology Medium 10602092

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proceedings of the National Academy of Sciences of the United States of America 1353 22451913
2011 Notch signalling in solid tumours: a little bit of everything but not all the time. Nature reviews. Cancer 675 21508972
2011 SIRPA is a specific cell-surface marker for isolating cardiomyocytes derived from human pluripotent stem cells. Nature biotechnology 401 22020386
2007 Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells. Nature immunology 401 17982459
2006 The SIRP family of receptors and immune regulation. Nature reviews. Immunology 338 16691243
1999 Integrin-associated protein is a ligand for the P84 neural adhesion molecule. The Journal of biological chemistry 286 9872987
2000 Regulation of Bcl-xL: a little bit of this and a little bit of STAT. Current opinion in oncology 199 11085453
2020 CD47 Ligation Repositions the Inhibitory Receptor SIRPA to Suppress Integrin Activation and Phagocytosis. Immunity 175 32768386
2008 Surfactant proteins A and D suppress alveolar macrophage phagocytosis via interaction with SIRP alpha. American journal of respiratory and critical care medicine 171 18420961
2005 p84, a new Gbetagamma-activated regulatory subunit of the type IB phosphoinositide 3-kinase p110gamma. Current biology : CB 137 15797027
2004 Human lymphocytes interact directly with CD47 through a novel member of the signal regulatory protein (SIRP) family. Journal of immunology (Baltimore, Md. : 1950) 130 15294972
1998 Integrin-mediated tyrosine phosphorylation of SHPS-1 and its association with SHP-2. Roles of Fak and Src family kinases. The Journal of biological chemistry 125 9582366
2015 Dihydroceramides: From Bit Players to Lead Actors. The Journal of biological chemistry 116 25947377
2013 Polymorphic Sirpa is the genetic determinant for NOD-based mouse lines to achieve efficient human cell engraftment. Blood 115 23293079
2000 SHPS-1 regulates integrin-mediated cytoskeletal reorganization and cell motility. The EMBO journal 115 11118207
2002 Negative regulation of platelet clearance and of the macrophage phagocytic response by the transmembrane glycoprotein SHPS-1. The Journal of biological chemistry 110 12167615
1998 Roles of the complex formation of SHPS-1 with SHP-2 in insulin-stimulated mitogen-activated protein kinase activation. The Journal of biological chemistry 105 9535915
2017 SIRPA-Inhibited, Marrow-Derived Macrophages Engorge, Accumulate, and Differentiate in Antibody-Targeted Regression of Solid Tumors. Current biology : CB 92 28669759
2002 SHPS-1, a multifunctional transmembrane glycoprotein. FEBS letters 87 12023008
2000 Inducible nitric oxide synthase: a little bit of good in all of us. Gut 86 10861252
1990 Central nervous system antigen P84 can serve as a substrate for neurite outgrowth. Developmental biology 83 2303162
2019 Engineering macrophages to phagocytose cancer cells by blocking the CD47/SIRPɑ axis. Cancer medicine 82 31183992
2002 Regulation of insulin-like growth factor I receptor dephosphorylation by SHPS-1 and the tyrosine phosphatase SHP-2. The Journal of biological chemistry 79 11779860
1998 Growth hormone regulation of SIRP and SHP-2 tyrosyl phosphorylation and association. The Journal of biological chemistry 79 9507023
2019 RRx-001 Acts as a Dual Small Molecule Checkpoint Inhibitor by Downregulating CD47 on Cancer Cells and SIRP-α on Monocytes/Macrophages. Translational oncology 78 30738349
1999 SHPS-1 is a scaffold for assembling distinct adhesion-regulated multi-protein complexes in macrophages. Current biology : CB 78 10469599
2020 Intracellular Entropy-Driven Multi-Bit DNA Computing for Tumor Progression Discrimination. Angewandte Chemie (International ed. in English) 77 32367682
2009 Selective control of SIRP-alpha-positive airway dendritic cell trafficking through CD47 is critical for the development of T(H)2-mediated allergic inflammation. The Journal of allergy and clinical immunology 75 19748659
2020 Just eat it: A review of CD47 and SIRP-α antagonism. Seminars in oncology 73 32517874
1997 The murine P84 neural adhesion molecule is SHPS-1, a member of the phosphatase-binding protein family. The Journal of neuroscience : the official journal of the Society for Neuroscience 73 9348339
1997 BIT, an immune antigen receptor-like molecule in the brain. FEBS letters 70 9271230
2003 A bit of give and take: the relationship between the extracellular matrix and the developing chondrocyte. Mechanisms of development 68 14623441
2008 CD47 in the immune response: role of thrombospondin and SIRP-alpha reverse signaling. Current drug targets 67 18855618
2017 Replication Study: The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. eLife 58 28100392
2015 SIRP/CD47 signaling in neurological disorders. Brain research 58 25795378
2000 Expression of a synapse-associated membrane protein, P84/SHPS-1, and its ligand, IAP/CD47, in mouse retina. The Journal of comparative neurology 58 10602092
2010 Correlated expression of CD47 and SIRPA in bone marrow and in peripheral blood predicts recurrence in breast cancer patients. Clinical cancer research : an official journal of the American Association for Cancer Research 56 20705613
2014 SIRPA, VCAM1 and CD34 identify discrete lineages during early human cardiovascular development. Stem cell research 53 24968096
2005 Human hHpr1/p84/Thoc1 regulates transcriptional elongation and physically links RNA polymerase II and RNA processing factors. Molecular and cellular biology 52 15870275
2003 A novel MyD-1 (SIRP-1alpha) signaling pathway that inhibits LPS-induced TNFalpha production by monocytes. Blood 51 12805067
2011 Differential roles for the p101 and p84 regulatory subunits of PI3Kγ in tumor growth and metastasis. Oncogene 47 21996737
2013 Split intein mediated ultra-rapid purification of tagless protein (SIRP). Biotechnology and bioengineering 45 23568256
1997 Mouse and human SHPS-1: molecular cloning of cDNAs and chromosomal localization of genes. Biochemical and biophysical research communications 45 9070220
2019 Come a little bit closer! Lipid droplet-ER contact sites are getting crowded. Biochimica et biophysica acta. Molecular cell research 44 31733263
2006 Influence of spatial resolution and bit depth on detection of small caries lesions with digital receptors. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics 44 17321456
2006 Thoc1/Hpr1/p84 is essential for early embryonic development in the mouse. Molecular and cellular biology 43 16705185
2004 Enrichment for a CD26hi SIRP- subset in lymph dendritic cells from the upper aero-digestive tract. Journal of leukocyte biology 40 15197234
2013 The BALB/c-specific polymorphic SIRPA enhances its affinity for human CD47, inhibiting phagocytosis against human cells to promote xenogeneic engraftment. Experimental hematology 39 24269920
2007 Small-cell lung cancer patients are just 'a little bit' tired: response shift and self-presentation in the measurement of fatigue. Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation 38 17450423
2017 Treg Cells Protect Dopaminergic Neurons against MPP+ Neurotoxicity via CD47-SIRPA Interaction. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 37 28268219
1999 Tyrosine phosphorylation and association of BIT with SHP-2 induced by neurotrophins. Journal of neurochemistry 37 10098842
2022 Tumor-intrinsic SIRPA promotes sensitivity to checkpoint inhibition immunotherapy in melanoma. Cancer cell 36 36332624
2011 An essential role for the association of CD47 to SHPS-1 in skeletal remodeling. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 36 21638321
2006 The chicken immunoregulatory receptor families SIRP, TREM, and CMRF35/CD300L. Immunogenetics 36 16493555
1997 Nested genetic bit analysis (N-GBA) for mutation detection in the p53 tumor suppressor gene. Nucleic acids research 34 9396817
2022 Scaling Up Multi-bit DNA Full Adder Circuits with Minimal Strand Displacement Reactions. Journal of the American Chemical Society 33 35603742
2004 Ectodomain shedding of SHPS-1 and its role in regulation of cell migration. The Journal of biological chemistry 33 15123722
1999 Gene structure of mouse BIT/SHPS-1. The Biochemical journal 33 10585853
2010 Role of the specific interaction of UL112-113 p84 with UL44 DNA polymerase processivity factor in promoting DNA replication of human cytomegalovirus. Journal of virology 31 20538862
2025 A RISC-V 32-bit microprocessor based on two-dimensional semiconductors. Nature 29 40175546
2023 SIRPA enhances osteosarcoma metastasis by stabilizing SP1 and promoting SLC7A3-mediated arginine uptake. Cancer letters 29 37769797
2000 SH2-B and SIRP: JAK2 binding proteins that modulate the actions of growth hormone. Recent progress in hormone research 29 11036942
1994 6-bit and 8-bit digital radiography for detecting simulated periodontal lesions. Oral surgery, oral medicine, and oral pathology 28 8015807
2023 Targeting CD47-SIRPa axis shows potent preclinical anti-tumor activity as monotherapy and synergizes with PARP inhibition. NPJ precision oncology 27 37468567
2021 Treating lymphoma is now a bit EZ-er. Blood advances 27 33904892
2016 Comparative Analysis of piggyBac, CRISPR/Cas9 and TALEN Mediated BAC Transgenesis in the Zygote for the Generation of Humanized SIRPA Rats. Scientific reports 27 27530248
2007 Novel structural determinants on SIRP alpha that mediate binding to CD47. Journal of immunology (Baltimore, Md. : 1950) 27 18025220
2016 "Marker of Self" CD47 on lentiviral vectors decreases macrophage-mediated clearance and increases delivery to SIRPA-expressing lung carcinoma tumors. Molecular therapy. Methods & clinical development 26 28053997
2011 A biclustering algorithm for extracting bit-patterns from binary datasets. Bioinformatics (Oxford, England) 26 21824973
2019 Eutopic endometrium from patients with endometriosis modulates the expression of CD36 and SIRP-α in peritoneal macrophages. The journal of obstetrics and gynaecology research 25 30843336
2008 Resistance to collagen-induced arthritis in SHPS-1 mutant mice. Biochemical and biophysical research communications 23 18455510
1998 Lysophosphatidic acid-induced association of SHP-2 with SHPS-1: roles of RHO, FAK, and a SRC family kinase. Oncogene 23 9662335
2004 Resistance of B16 melanoma cells to CD47-induced negative regulation of motility as a result of aberrant N-glycosylation of SHPS-1. The Journal of biological chemistry 21 14739297
2020 A human SIRPA knock-in xenograft mouse model to study human hematopoietic and cancer stem cells. Blood 20 32206775
2018 Making glycoproteins a little bit sweeter with PDB-REDO. Acta crystallographica. Section F, Structural biology communications 20 30084395
2022 MicroRNA-382 Promotes M2-Like Macrophage via the SIRP-α/STAT3 Signaling Pathway in Aristolochic Acid-Induced Renal Fibrosis. Frontiers in immunology 19 35585990
2016 Specific carotenoid pigments in the diet and a bit of oxidative stress in the recipe for producing red carotenoid-based signals. PeerJ 19 27635308
2005 Non-reciprocal chromosomal bridge-induced translocation (BIT) by targeted DNA integration in yeast. Chromosoma 19 15843952
2022 Lack of SIRP-alpha reduces lung cancer growth in mice by promoting anti-tumour ability of macrophages and neutrophils. Cell proliferation 18 36419386
2020 Gβγ is a direct regulator of endogenous p101/p110γ and p84/p110γ PI3Kγ complexes in mouse neutrophils. Science signaling 18 33144519
2019 A little bit of sex prevents mutation accumulation even in apomictic polyploid plants. BMC evolutionary biology 18 31412772
2008 Negative regulation by SHPS-1 of Toll-like receptor-dependent proinflammatory cytokine production in macrophages. Genes to cells : devoted to molecular & cellular mechanisms 18 18233962
2007 Structural insight into the specific interaction between murine SHPS-1/SIRP alpha and its ligand CD47. Journal of molecular biology 18 18045614
2000 Molecular cloning of a novel human gene (SIRP-B2) which encodes a new member of the SIRP/SHPS-1 protein family. Journal of human genetics 18 11185750
2019 PEX10, SIRPA-SIRPG, and SOX5 gene polymorphisms are strongly associated with nonobstructive azoospermia susceptibility. Journal of assisted reproduction and genetics 17 30863997
2008 Essential roles of SHPS-1 in induction of contact hypersensitivity of skin. Immunology letters 17 18809435
2003 Regulation of multiple functions of SHPS-1, a transmembrane glycoprotein, by its cytoplasmic region. Biochemical and biophysical research communications 17 12963030
2024 Partitioning of a 2-bit hash function across 66 communicating cells. Nature chemical biology 16 39317847
2008 Multi-bit biomemory consisting of recombinant protein variants, azurin. Biosensors & bioelectronics 16 18809307
2007 Lineage-specific transcription factors in multipotent hematopoietic progenitors: a little bit goes a long way. Cell cycle (Georgetown, Tex.) 16 17457053
2024 DNA-Programmed Four-Bit Quaternary Fluorescence Encoding (FLUCO) Enables 51-Colored Bioimaging Analysis. Journal of the American Chemical Society 15 38859621
2003 Ubiquitination-mediated regulation of biosynthesis of the adhesion receptor SHPS-1 in response to endoplasmic reticulum stress. The Journal of biological chemistry 15 14701835
2022 Soluble SIRP-Alpha Promotes Murine Acute Lung Injury Through Suppressing Macrophage Phagocytosis. Frontiers in immunology 14 35634325
2017 Prostate cancer downregulated SIRP-α modulates apoptosis and proliferation through p38-MAPK/NF-κB/COX-2 signaling. Oncology letters 14 28588738
2010 PDK1 recruitment to the SHPS-1 signaling complex enhances insulin-like growth factor-i-stimulated AKT activation and vascular smooth muscle cell survival. The Journal of biological chemistry 14 20643654
2021 It's a small bit of advice, but actually on the day, made such a difference…: perceptions of quality in abortion care in England and Wales. Reproductive health 13 34743705
2019 Novel 2, 8-bit derivatives of quinolines attenuate Pseudomonas aeruginosa virulence and biofilm formation. Bioorganic & medicinal chemistry letters 13 30630718
2023 The Atomic Drill Bit: Precision Controlled Atomic Fabrication of 2D Materials. Advanced materials (Deerfield Beach, Fla.) 12 36635517
2023 Molecular basis for differential activation of p101 and p84 complexes of PI3Kγ by Ras and GPCRs. Cell reports 12 36842083
2016 SIRP Alpha Protein Downregulates in Human Astrocytoma: Presumptive Involvement of Hsa-miR-520d-5p and Hsa-miR-520d-3p. Molecular neurobiology 12 27900675