Gene Symbol: Sirpa
Description: signal-regulatory protein alpha
Alias: AI835480, Bit, CD172a, P84, Ptpns1, SHP-1, SHPS-1, SIRP, tyrosine-protein phosphatase non-receptor type substrate 1, CD172 antigen-like family member A, SHP substrate 1, brain Ig-like molecule with tyrosine-based activation motifs, brain immunological-like with tyrosine-based motifs, inhibitory receptor SHPS-1, mSIRP-alpha1, myD-1 antigen, protein tyrosine phosphatase, non-receptor type substrate 1, signal-regulatory protein alpha-1, sirp-alpha-1
Species: mouse
Products:     Sirpa

Top Publications

  1. Kong X, Yan H, Chen L, Dong L, Yang W, Liu Q, et al. LPS-induced down-regulation of signal regulatory protein {alpha} contributes to innate immune activation in macrophages. J Exp Med. 2007;204:2719-31 pubmed
    ..Signal regulatory protein (SIRP) alpha, a member of the SIRP family that is abundantly expressed in macrophages, has been implicated in regulating ..
  2. Fujioka Y, Matozaki T, Noguchi T, Iwamatsu A, Yamao T, Takahashi N, et al. A novel membrane glycoprotein, SHPS-1, that binds the SH2-domain-containing protein tyrosine phosphatase SHP-2 in response to mitogens and cell adhesion. Mol Cell Biol. 1996;16:6887-99 pubmed
    ..The predicted amino acid sequence of the encoded protein, termed SHPS-1 (SHP substrate 1), suggests that it is a glycosylated receptor-like protein with three immunoglobulin-like domains in its ..
  3. Neznanov N, Neznanova L, Kondratov R, Burdelya L, Kandel E, O Rourke D, et al. Dominant negative form of signal-regulatory protein-alpha (SIRPalpha /SHPS-1) inhibits tumor necrosis factor-mediated apoptosis by activation of NF-kappa B. J Biol Chem. 2003;278:3809-15 pubmed
    ..These data indicate that SIRPalpha/SHPS-1 is involved in negative regulation of NF-kappaB signaling. ..
  4. Raymond M, Van V, Rubio M, Welzenbach K, Sarfati M. Targeting SIRP-? protects from type 2-driven allergic airway inflammation. Eur J Immunol. 2010;40:3510-8 pubmed publisher
    ..CD47 and its receptor, signal regulatory protein ? (SIRP-?), govern innate cell trafficking...
  5. Ikeda H, Okazawa H, Ohnishi H, Murata Y, Oldenborg P, Matozaki T. Mutational analysis of the mechanism of negative regulation by SRC homology 2 domain-containing protein tyrosine phosphatase substrate-1 of phagocytosis in macrophages. J Immunol. 2006;177:3123-32 pubmed
    ..Moreover, SHPS-1 may regulate the attachment of RBCs to macrophages by an as yet unidentified mechanism. ..
  6. Legrand N, Huntington N, Nagasawa M, Bakker A, Schotte R, Strick Marchand H, et al. Functional CD47/signal regulatory protein alpha (SIRP(alpha)) interaction is required for optimal human T- and natural killer- (NK) cell homeostasis in vivo. Proc Natl Acad Sci U S A. 2011;108:13224-9 pubmed publisher
    ..Interactions between signal regulatory protein alpha (SIRP?; expressed on phagocytes) and CD47 (expressed on hematopoietic cells) negatively regulate phagocyte activity of ..
  7. Ohnishi H, Kobayashi H, Okazawa H, Ohe Y, Tomizawa K, Sato R, et al. Ectodomain shedding of SHPS-1 and its role in regulation of cell migration. J Biol Chem. 2004;279:27878-87 pubmed
    ..These results suggest that shedding of the ectodomain of SHPS-1 plays an important role in regulation of cell migration and spreading by this protein. ..
  8. Jiang P, Lagenaur C, Narayanan V. Integrin-associated protein is a ligand for the P84 neural adhesion molecule. J Biol Chem. 1999;274:559-62 pubmed
    P84 (also known as SHPS-1, BIT, and SIRP) is a heterophilic adhesive membrane protein involved in receptor tyrosine kinase signaling that is found at synapses in the mammalian central nervous system and in non-neural tissues...
  9. Takenaka K, Prasolava T, Wang J, Mortin Toth S, Khalouei S, Gan O, et al. Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells. Nat Immunol. 2007;8:1313-23 pubmed
    ..We used positional genetics to characterize the molecular basis for this strain specificity and found that the NOD Sirpa allele conferred support for human hematopoiesis...

More Information


  1. Sano S, Ohnishi H, Kubota M. Gene structure of mouse BIT/SHPS-1. Biochem J. 1999;344 Pt 3:667-75 pubmed
    b>BIT/SHPS-1/SIRPalpha/P84 is a unique molecule with a high degree of homology with immune antigen recognition molecules (immunoglobulin, T-cell receptor and MHC), and is highly expressed in the brain...
  2. Okuzawa C, Kaneko Y, Murata Y, Miyake A, Saito Y, Okajo J, et al. Resistance to collagen-induced arthritis in SHPS-1 mutant mice. Biochem Biophys Res Commun. 2008;371:561-6 pubmed publisher
    ..The CII-induced proliferation of, and production of cytokines by, T cells from immunized SHPS-1 mutant mice were reduced compared to wild-type cells. These results suggest that SHPS-1 is essential for development of CIA. ..
  3. Saito Y, Iwamura H, Kaneko T, Ohnishi H, Murata Y, Okazawa H, et al. Regulation by SIRP? of dendritic cell homeostasis in lymphoid tissues. Blood. 2010;116:3517-25 pubmed publisher
    ..Signal regulatory protein ? (SIRP?), an immunoglobulin superfamily protein that is predominantly expressed in DCs, mediates cell-cell signaling by ..
  4. Yamauchi T, Takenaka K, Urata S, Shima T, Kikushige Y, Tokuyama T, et al. Polymorphic Sirpa is the genetic determinant for NOD-based mouse lines to achieve efficient human cell engraftment. Blood. 2013;121:1316-25 pubmed publisher
    ..Our positional genetic study has located the NOD-specific polymorphic Sirpa as a molecule responsible for its high xenograft efficiency: it recognizes human CD47 and the resultant signaling ..
  5. Murai Takebe R, Noguchi T, Ogura T, Mikami T, Yanagi K, Inagaki K, et al. Ubiquitination-mediated regulation of biosynthesis of the adhesion receptor SHPS-1 in response to endoplasmic reticulum stress. J Biol Chem. 2004;279:11616-25 pubmed publisher
    ..An NFB42 mutant lacking the F box domain had no such effects. Our results suggest that SCF(NFB42) regulates SHPS-1 biosynthesis in response to ER stress...
  6. Kobayashi M, Ohnishi H, Okazawa H, Murata Y, Hayashi Y, Kobayashi H, et al. Expression of Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 in pancreatic beta-Cells and its role in promotion of insulin secretion and protection against diabetes. Endocrinology. 2008;149:5662-9 pubmed publisher
    ..Preventing of alpha2-adrenergic receptor-mediated inhibition of insulin secretion may partly participate in such a function of SHPS-1. ..
  7. Motegi S, Okazawa H, Murata Y, Kanazawa Y, Saito Y, Kobayashi H, et al. Essential roles of SHPS-1 in induction of contact hypersensitivity of skin. Immunol Lett. 2008;121:52-60 pubmed publisher
    ..However, such regulation by SHPS-1 does not appear to require its interaction with CD47. ..
  8. Gardai S, Xiao Y, Dickinson M, Nick J, Voelker D, Greene K, et al. By binding SIRPalpha or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation. Cell. 2003;115:13-23 pubmed
    ..However, interaction of these heads with PAMPs on foreign organisms or damaged cells and presentation of the collagenous tails in an aggregated state to calreticulin/CD91, stimulates phagocytosis and proinflammatory responses. ..
  9. Umemori H, Sanes J. Signal regulatory proteins (SIRPS) are secreted presynaptic organizing molecules. J Biol Chem. 2008;283:34053-61 pubmed publisher
    ..A major bioactive species was the extracellular domain of signal regulatory protein alpha (SIRP-alpha), a transmembrane immunoglobulin superfamily member concentrated at synapses...
  10. Barclay A. Signal regulatory protein alpha (SIRPalpha)/CD47 interaction and function. Curr Opin Immunol. 2009;21:47-52 pubmed publisher
    ..The interaction may be modified by endocytosis of the receptors, cleavage by proteolysis and through interactions of surfactant proteins. ..
  11. Ohnishi H, Murata T, Kusakari S, Hayashi Y, Takao K, Maruyama T, et al. Stress-evoked tyrosine phosphorylation of signal regulatory protein ? regulates behavioral immobility in the forced swim test. J Neurosci. 2010;30:10472-83 pubmed publisher
    ..Thus, tyrosine phosphorylation of SIRPalpha is important for regulation of depression-like behavior in the response of the brain to stress. ..
  12. Yamao T, Noguchi T, Takeuchi O, Nishiyama U, Morita H, Hagiwara T, et al. Negative regulation of platelet clearance and of the macrophage phagocytic response by the transmembrane glycoprotein SHPS-1. J Biol Chem. 2002;277:39833-9 pubmed
    ..These results indicate that SHPS-1 both contributes to the survival of circulating platelets and down-regulates the macrophage phagocytic response. ..
  13. Iwamura H, Saito Y, Sato Hashimoto M, Ohnishi H, Murata Y, Okazawa H, et al. Essential roles of SIRP? in homeostatic regulation of skin dendritic cells. Immunol Lett. 2011;135:100-7 pubmed publisher
    Signal regulatory protein ? (SIRP?) is an immunoglobulin superfamily protein that is predominantly expressed in dendritic cells (DCs)...
  14. Kanazawa Y, Saito Y, Supriatna Y, Tezuka H, Kotani T, Murata Y, et al. Role of SIRP? in regulation of mucosal immunity in the intestine. Genes Cells. 2010;15:1189-200 pubmed publisher
    ..Signal regulatory protein ? (SIRP?) is a transmembrane protein that is specifically expressed in DCs, macrophages and neutrophils...
  15. Inagaki K, Yamao T, Noguchi T, Matozaki T, Fukunaga K, Takada T, et al. SHPS-1 regulates integrin-mediated cytoskeletal reorganization and cell motility. EMBO J. 2000;19:6721-31 pubmed
  16. Atibalentja D, Murphy K, Unanue E. Functional redundancy between thymic CD8?+ and Sirp?+ conventional dendritic cells in presentation of blood-derived lysozyme by MHC class II proteins. J Immunol. 2011;186:1421-31 pubmed publisher
    ..Two conventional dendritic cells (cDCs), the CD8?(+)Sirp?(-)CD11c(hi) (CD8?(+) cDC) and the CD8?(-)Sirp?(+)CD11c(hi) (Sirp?(+) cDC), were previously identified as ..
  17. Veillette A, Thibaudeau E, Latour S. High expression of inhibitory receptor SHPS-1 and its association with protein-tyrosine phosphatase SHP-1 in macrophages. J Biol Chem. 1998;273:22719-28 pubmed
    SHPS-1 (or SIRP) is a member of the immunoglobulin (Ig) superfamily abundantly expressed in neurons and other cell types...
  18. Baba T, Nakamoto Y, Mukaida N. Crucial contribution of thymic Sirp alpha+ conventional dendritic cells to central tolerance against blood-borne antigens in a CCR2-dependent manner. J Immunol. 2009;183:3053-63 pubmed publisher
    ..Given their intrathymic cortical localization, CD11c(+)B220(-)CD8alpha(-)Sirpalpha(+) cDCs can have a unique role in the development of central tolerance against circulating peripheral Ags, at least partially in a CCR2-dependent manner. ..
  19. Chuang W, Lagenaur C. Central nervous system antigen P84 can serve as a substrate for neurite outgrowth. Dev Biol. 1990;137:219-32 pubmed
    ..Using this method, we have identified a unique cell surface antigen, designated P84, as a new neural cell adhesion molecule...
  20. Okazawa H, Motegi S, Ohyama N, Ohnishi H, Tomizawa T, Kaneko Y, et al. Negative regulation of phagocytosis in macrophages by the CD47-SHPS-1 system. J Immunol. 2005;174:2004-11 pubmed
    ..The inhibition of phagocytosis by the SHPS-1-SHP-1 complex may be mediated at the level of Syk or PI3K signaling. ..
  21. Tomizawa T, Kaneko Y, Kaneko Y, Saito Y, Ohnishi H, Okajo J, et al. Resistance to experimental autoimmune encephalomyelitis and impaired T cell priming by dendritic cells in Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 mutant mice. J Immunol. 2007;179:869-77 pubmed
    ..These results show that SHPS-1 on DCs is essential for priming of naive T cells and the development of EAE. SHPS-1 is thus a potential therapeutic target in inflammatory disorders of the CNS and other autoimmune diseases. ..
  22. Okajo J, Kaneko Y, Murata Y, Tomizawa T, Okuzawa C, Saito Y, et al. Regulation by Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 of alpha-galactosylceramide-induced antimetastatic activity and Th1 and Th2 responses of NKT cells. J Immunol. 2007;178:6164-72 pubmed
    ..Moreover, our recent findings suggest that SHPS-1 on DCs is also essential for the priming of CD4+ T cells by DCs. ..
  23. Fukunaga A, Nagai H, Yu X, Oniki S, Okazawa H, Motegi S, et al. Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 regulates the induction of Langerhans cell maturation. Eur J Immunol. 2006;36:3216-26 pubmed
    ..These observations indicate that SHPS-1 plays an important role in the maturation of LC ex vivo and in vivo, and that SHPS-1-CD47 interaction may negatively regulate CHS. ..
  24. Johansen M, Brown E. Dual regulation of SIRPalpha phosphorylation by integrins and CD47. J Biol Chem. 2007;282:24219-30 pubmed
    ..This shows that SIRPalpha phosphorylation is dually regulated and demonstrates a new mechanism for functional cooperation between integrins and the integrin-associated protein CD47. ..
  25. Xu M, Pu Y, Han D, Shi Y, Cao X, Liang H, et al. Dendritic Cells but Not Macrophages Sense Tumor Mitochondrial DNA for Cross-priming through Signal Regulatory Protein ? Signaling. Immunity. 2017;47:363-373.e5 pubmed publisher
    ..Here we have shown that CD47-signal regulatory protein ? (SIRP?) axis dictates the fate of ingested DNA in DCs for immune evasion...
  26. Nuvolone M, Paolucci M, Sorce S, Kana V, Moos R, Matozaki T, et al. Prion pathogenesis is unaltered in the absence of SIRP?-mediated "don't-eat-me" signaling. PLoS ONE. 2017;12:e0177876 pubmed publisher
    ..of signal regulatory protein ? (SIRP?), a key modulator of host cell phagocytosis; SIRP? is encoded by the Sirpa gene that is genetically linked to the prion gene Prnp...
  27. Amin A, Ichigotani Y, Oo M, Biswas M, Yuan H, Huang P, et al. The PLC-PKC cascade is required for IL-1beta-dependent Erk and Akt activation: their role in proliferation. Int J Oncol. 2003;23:1727-31 pubmed
    ..Taken together, our results suggest that a SHPS-1-PLC-gamma complex activate the PLC-PKC cascade, which is required for the activation of IL-1beta-dependent Erk and Akt signalings and cell proliferation. ..
  28. Tanaka T, Fujita Y, Ueno M, Shultz L, Yamashita T. Suppression of SHP-1 promotes corticospinal tract sprouting and functional recovery after brain injury. Cell Death Dis. 2013;4:e567 pubmed publisher
    ..Motor function recovery of impaired forelimb was enhanced in +/me(v) mice. Collectively, our results indicate that downregulation of SHP-1 activity promotes corticospinal tract sprouting and functional recovery after brain injury. ..
  29. Nakaishi A, Hirose M, Yoshimura M, Oneyama C, Saito K, Kuki N, et al. Structural insight into the specific interaction between murine SHPS-1/SIRP alpha and its ligand CD47. J Mol Biol. 2008;375:650-60 pubmed
    SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1 (SHPS-1 or SIRP alpha/BIT) is an immunoglobulin (Ig) superfamily transmembrane receptor and a member of the signal regulatory protein (SIRP) family involved in cell-..
  30. Lv Z, Bian Z, Shi L, Niu S, Ha B, Tremblay A, et al. Loss of Cell Surface CD47 Clustering Formation and Binding Avidity to SIRPα Facilitate Apoptotic Cell Clearance by Macrophages. J Immunol. 2015;195:661-71 pubmed publisher
    CD47, a self recognition marker expressed on tissue cells, interacts with immunoreceptor SIRPα expressed on the surface of macrophages to initiate inhibitory signaling that prevents macrophage phagocytosis of healthy host cells...
  31. Watanabe N, Gavrieli M, Sedy J, Yang J, Fallarino F, Loftin S, et al. BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1. Nat Immunol. 2003;4:670-9 pubmed
    ..B7x, a peripheral homolog of B7, is a ligand of BTLA. Thus, BTLA is a third inhibitory receptor on T lymphocytes with similarities to cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1). ..
  32. Huang Y, Liu Z, Cao B, Qiu Y, Peng Y. Treg Cells Protect Dopaminergic Neurons against MPP+ Neurotoxicity via CD47-SIRPA Interaction. Cell Physiol Biochem. 2017;41:1240-1254 pubmed publisher
    ..neurotoxicity via an interaction between the two transmembrane proteins CD47 and signal regulatory protein ? (SIRPA). Primary ventral mesencephalic (VM) cells or VM neurons were pretreated with Treg cells before MPP+ treatment...
  33. Rugg Gunn P, Cox B, Lanner F, Sharma P, Ignatchenko V, McDonald A, et al. Cell-surface proteomics identifies lineage-specific markers of embryo-derived stem cells. Dev Cell. 2012;22:887-901 pubmed publisher
    ..These results provide a comprehensive stem cell proteomic resource and enable new approaches to interrogate the mechanisms that regulate cell fate specification. ..
  34. Ayi K, Lu Z, Serghides L, Ho J, Finney C, Wang J, et al. CD47-SIRPα Interactions Regulate Macrophage Uptake of Plasmodium falciparum-Infected Erythrocytes and Clearance of Malaria In Vivo. Infect Immun. 2016;84:2002-2011 pubmed publisher
    CD47 engagement by the macrophage signal regulatory protein alpha (SIRPα) inhibits phagocytic activity and protects red blood cells (RBCs) from erythrophagocytosis...
  35. Guo Y, Liu D, Bian Z, Zhang C, Zen K. Down-regulation of platelet surface CD47 expression in Escherichia coli O157:H7 infection-induced thrombocytopenia. PLoS ONE. 2009;4:e7131 pubmed publisher
  36. Maile L, DeMambro V, Wai C, Lotinun S, Aday A, Capps B, et al. An essential role for the association of CD47 to SHPS-1 in skeletal remodeling. J Bone Miner Res. 2011;26:2068-81 pubmed publisher
  37. Ott V, Tamir I, Niki M, Pandolfi P, Cambier J. Downstream of kinase, p62(dok), is a mediator of Fc gamma IIB inhibition of Fc epsilon RI signaling. J Immunol. 2002;168:4430-9 pubmed
    ..Taken together, these data suggest a role for p62(dok) as a mediator of Fc gamma RIIB inhibition of Fc epsilon RI signal transduction in mast cells. ..
  38. Ehringer M, Thompson J, Conroy O, Yang F, Hink R, Bennett B, et al. Fine mapping of polymorphic alcohol-related quantitative trait loci candidate genes using interval-specific congenic recombinant mice. Alcohol Clin Exp Res. 2002;26:1603-8 pubmed
  39. Yu W, Hawley T, Hawley R, Qu C. Role of the docking protein Gab2 in beta(1)-integrin signaling pathway-mediated hematopoietic cell adhesion and migration. Blood. 2002;99:2351-9 pubmed
    ..Taken together, these results suggest an important signaling role for Gab2 in regulating hematopoietic cell adhesion and migration. ..
  40. Duchesne C, Charland S, Asselin C, Nahmias C, Rivard N. Negative regulation of beta-catenin signaling by tyrosine phosphatase SHP-1 in intestinal epithelial cells. J Biol Chem. 2003;278:14274-83 pubmed
    ..Taken together, our results indicate that SHP-1 may be involved in the regulation of beta-catenin transcriptional function and in the negative control of intestinal epithelial cell proliferation. ..
  41. Sato Hashimoto M, Saito Y, Ohnishi H, Iwamura H, Kanazawa Y, Kaneko T, et al. Signal regulatory protein ? regulates the homeostasis of T lymphocytes in the spleen. J Immunol. 2011;187:291-7 pubmed publisher
    ..Signal regulatory protein ? (SIRP?), an Ig superfamily protein that is predominantly expressed in dendritic cells or macrophages, mediates cell-cell ..
  42. Sobota R, Müller P, Khouri C, Ullrich A, Poli V, Noguchi T, et al. SHPS-1/SIRP1alpha contributes to interleukin-6 signalling. Cell Signal. 2008;20:1385-91 pubmed publisher
    ..Our observations will help to understand the tight balance of MAPK- and STAT3-activation in response to IL-6 which was found to be misbalanced in many autoimmune diseases, inflammatory proliferative diseases and cancer. ..
  43. Marschinke F, Hashemian S, Matozaki T, Oldenborg P, Stromberg I. The absence of CD47 promotes nerve fiber growth from cultured ventral mesencephalic dopamine neurons. PLoS ONE. 2012;7:e45218 pubmed publisher
    ..CD47 serves as a ligand for signal regulatory protein (SIRP) ? and as a receptor for the extracellular matrix protein thrombospondin-1 (TSP-1)...
  44. Washio K, Kotani T, Saito Y, Respatika D, Murata Y, Kaneko Y, et al. Dendritic cell SIRPα regulates homeostasis of dendritic cells in lymphoid organs. Genes Cells. 2015;20:451-63 pubmed publisher
    ..Thus, we here generated the mice, in which SIRPα was specifically ablated in CD11c(+) DCs (Sirpa(Δ) (DC) )...
  45. Tsai R, Rodriguez P, Discher D. Self inhibition of phagocytosis: the affinity of 'marker of self' CD47 for SIRPalpha dictates potency of inhibition but only at low expression levels. Blood Cells Mol Dis. 2010;45:67-74 pubmed publisher
    ..Quantitative analyses here prompt more complete characterizations of both CD47 levels and SIRPalpha polymorphisms when attempting to study in vivo effects of these key proteins in innate immunity. ..
  46. Schaefer L, Beermann M, Miller J. Coding sequence, genomic organization, chromosomal localization, and expression pattern of the signalosome component Cops2: the mouse homologue of Drosophila alien. Genomics. 1999;56:310-6 pubmed
    ..9-kb band in liver. Immunostaining of native and epitope tagged proteins localized the mouse Cops2 protein in both the cytoplasm and the nucleus, with larger amounts in the nucleus in some cells. ..
  47. Jiang D, Zhang X, Gao L, Zong J, Zhou H, Liu Y, et al. Signal regulatory protein-? protects against cardiac hypertrophy via the disruption of toll-like receptor 4 signaling. Hypertension. 2014;63:96-104 pubmed publisher
    Signal regulatory protein-? (SIRPA/SIRP?) is a transmembrane protein that is expressed in various tissues, including the heart...
  48. Wishcamper C, Brooks D, Douglas Coffin J, Lurie D. Focal cerebral ischemia upregulates SHP-1 in reactive astrocytes in juvenile mice. Brain Res. 2003;974:88-98 pubmed
    ..These results suggest that SHP-1 plays an important role in the regulation of glial activation and proliferation in the ischemic CNS. ..
  49. Chung D, Humphrey M, Nakamura M, Ginzinger D, Seaman W, Daws M. CMRF-35-like molecule-1, a novel mouse myeloid receptor, can inhibit osteoclast formation. J Immunol. 2003;171:6541-8 pubmed
    ..Thus, we define a new family of myeloid receptors, and demonstrate that the first member of this family, CLM-1, is an inhibitory receptor, able to block osteoclastogenesis. ..
  50. Bian Z, Shi L, Guo Y, Lv Z, Tang C, Niu S, et al. Cd47-Sirp? interaction and IL-10 constrain inflammation-induced macrophage phagocytosis of healthy self-cells. Proc Natl Acad Sci U S A. 2016;113:E5434-43 pubmed publisher which CD47 is the ubiquitous marker of self, and its interaction with macrophage signal regulatory protein ? (SIRP?) triggers inhibitory signaling through SIRP? cytoplasmic immunoreceptor tyrosine-based inhibition motifs and ..
  51. Washington A, Quigley L, McVicar D. Initial characterization of TREM-like transcript (TLT)-1: a putative inhibitory receptor within the TREM cluster. Blood. 2002;100:3822-4 pubmed
    ..Based on these characteristics, it is likely that TLT-1 regulates the signaling of the TREM family receptors. ..
  52. Kim C, Qu C, Hangoc G, Cooper S, Anzai N, Feng G, et al. Abnormal chemokine-induced responses of immature and mature hematopoietic cells from motheaten mice implicate the protein tyrosine phosphatase SHP-1 in chemokine responses. J Exp Med. 1999;190:681-90 pubmed
    ..However, expression of some chemokine receptors (CCR1, CCR2, CCR3, and CXCR2) was significantly enhanced in me(v)/me(v) T cells. Our results implicate SHP-1 involvement in a number of different chemokine-induced biological activities. ..
  53. Alvarez Zarate J, Matlung H, Matozaki T, Kuijpers T, Maridonneau Parini I, van den Berg T. Regulation of Phagocyte Migration by Signal Regulatory Protein-Alpha Signaling. PLoS ONE. 2015;10:e0127178 pubmed publisher
    Signaling through the inhibitory receptor signal regulatory protein-alpha (SIRPα) controls effector functions in phagocytes...
  54. Maruyama T, Kusakari S, Sato Hashimoto M, Hayashi Y, Kotani T, Murata Y, et al. Hypothermia-induced tyrosine phosphorylation of SIRP? in the brain. J Neurochem. 2012;121:891-902 pubmed publisher
    Signal regulatory protein ? (SIRP?) is a neuronal membrane protein that undergoes tyrosine phosphorylation in the brain of mice in response to forced swim (FS) stress in cold water, and this response is implicated in regulation of ..
  55. Baba T, Badr M, Tomaru U, Ishizu A, Mukaida N. Novel process of intrathymic tumor-immune tolerance through CCR2-mediated recruitment of Sirp?+ dendritic cells: a murine model. PLoS ONE. 2012;7:e41154 pubmed publisher
    ..We previously demonstrated that a minor thymic conventional dendritic cell (cDC) subset, CD8?(-)Sirp?(+) cDCs, but not the major subset, CD8?(+)Sirp?(-) cDCs can selectively capture blood-borne antigens and crucially ..
  56. Miyake A, Murata Y, Okazawa H, Ikeda H, Niwayama Y, Ohnishi H, et al. Negative regulation by SHPS-1 of Toll-like receptor-dependent proinflammatory cytokine production in macrophages. Genes Cells. 2008;13:209-19 pubmed publisher
    ..SHPS-1 then negatively regulates TLR4- or TLR3-dependent cytokine production through inhibition of NF-kappaB-dependent signaling. ..
  57. Sano S, Ohnishi H, Omori A, Hasegawa J, Kubota M. BIT, an immune antigen receptor-like molecule in the brain. FEBS Lett. 1997;411:327-34 pubmed
    ..The overall structure is similar to those of immune antigen receptors. This molecule, BIT (brain immunoglobulin-like molecule with TAMs), is a major endogenous substrates of brain tyrosine kinases in vitro...
  58. Yamao T, Matozaki T, Amano K, Matsuda Y, Takahashi N, Ochi F, et al. Mouse and human SHPS-1: molecular cloning of cDNAs and chromosomal localization of genes. Biochem Biophys Res Commun. 1997;231:61-7 pubmed
    ..0 centimorgans distal and 1.4 centimorgans proximal to the microsatellite markers D2Mit63 and D2Mit19, respectively, in a region associated with the mutations coloboma (Cm), lethal milk (lm), and well-haarig (we). ..
  59. Liu H, Chen F, Wu W, Cao A, Xue X, Yao S, et al. TLR5 mediates CD172α(+) intestinal lamina propria dendritic cell induction of Th17 cells. Sci Rep. 2016;6:22040 pubmed publisher
    ..Wild-type CD172α(+), but not CD172α(-), LPDCs induced Th17 cells, whereas TLR5-deficient LPDC did not induce Th17 cells. Our data thereby demonstrated that TLR5 mediates CD172α(+)LPDC induction of Th17 cells in the intestines. ..
  60. Ho C, Guo N, Sockolosky J, Ring A, Weiskopf K, Özkan E, et al. "Velcro" engineering of high affinity CD47 ectodomain as signal regulatory protein α (SIRPα) antagonists that enhance antibody-dependent cellular phagocytosis. J Biol Chem. 2015;290:12650-63 pubmed publisher
    ..known as the "don't-eat-me" signal, to macrophages upon engaging its receptor signal regulatory protein α (SIRPα)...
  61. Ohnishi H, Kubota M, Sano S. BIT (Bit) maps to mouse chromosome 2. Genomics. 1997;40:504-6 pubmed
  62. Subramanian S, Tsai R, Sen S, Dahl K, Discher D. Membrane mobility and clustering of Integrin Associated Protein (IAP, CD47)--major differences between mouse and man and implications for signaling. Blood Cells Mol Dis. 2006;36:364-72 pubmed
    ..The results thus highlight major species differences in CD47-SIRPalpha interactions and CD47 integration, suggesting that signaling by CD47 in man may be qualitatively different from mouse. ..
  63. Stofega M, Wang H, Ullrich A, Carter Su C. Growth hormone regulation of SIRP and SHP-2 tyrosyl phosphorylation and association. J Biol Chem. 1998;273:7112-7 pubmed
    ..These results suggest that SIRPalpha is a signaling molecule for GH but not for LIF or IFNgamma. Differential phosphorylation of SIRPalpha and SHP-2 may contribute to the distinct physiological effects of these ligands. ..
  64. Radhakrishnan Y, Busby W, Shen X, Maile L, Clemmons D. Insulin-like growth factor-I-stimulated insulin receptor substrate-1 negatively regulates Src homology 2 domain-containing protein-tyrosine phosphatase substrate-1 function in vascular smooth muscle cells. J Biol Chem. 2010;285:15682-95 pubmed publisher
    ..We conclude that IRS-1 is an important factor for maintaining VSMCs in the non-proliferative state and that its down-regulation is a component of the VSMC response to hyperglycemic stress that results in an enhanced response to IGF-I. ..
  65. Ogura T, Noguchi T, Murai Takebe R, Hosooka T, Honma N, Kasuga M. Resistance of B16 melanoma cells to CD47-induced negative regulation of motility as a result of aberrant N-glycosylation of SHPS-1. J Biol Chem. 2004;279:13711-20 pubmed
    ..Resistance to this inhibitory mechanism may contribute to the highly metastatic potential of B16 melanoma. ..
  66. Koskinen C, Persson E, Baldock P, Stenberg A, Boström I, Matozaki T, et al. Lack of CD47 impairs bone cell differentiation and results in an osteopenic phenotype in vivo due to impaired signal regulatory protein ? (SIRP?) signaling. J Biol Chem. 2013;288:29333-44 pubmed publisher
    ..CD47 is a ligand for SIRP? (signal regulatory protein ?), which showed strongly reduced tyrosine phosphorylation in CD47(-/-) bone marrow ..
  67. Zhou D, Collins C, Wu P, Brown E. Protein tyrosine phosphatase SHP-1 positively regulates TLR-induced IL-12p40 production in macrophages through inhibition of phosphatidylinositol 3-kinase. J Leukoc Biol. 2010;87:845-55 pubmed publisher
  68. Tada K, Tanaka M, Hanayama R, Miwa K, Shinohara A, Iwamatsu A, et al. Tethering of apoptotic cells to phagocytes through binding of CD47 to Src homology 2 domain-bearing protein tyrosine phosphatase substrate-1. J Immunol. 2003;171:5718-26 pubmed
    ..These results indicate that macrophages require CD47 and phosphatidylserine on apoptotic cells for engulfment, and suggest that the interaction between CD47 and SHPS-1 works as a tethering step in the phagocytosis. ..
  69. Dong L, Kong X, Yan H, Yu L, Chen L, Yang W, et al. Signal regulatory protein alpha negatively regulates both TLR3 and cytoplasmic pathways in type I interferon induction. Mol Immunol. 2008;45:3025-35 pubmed publisher
    ..Here we show that signal regulatory protein (SIRP) alpha negatively regulates both TLR3- and RIG-1/MDA5-dependent anti-viral pathways...
  70. Holm C, Engman S, Sulniute R, Matozaki T, Oldenborg P, Lundberg P. Lack of SIRP? phosphorylation and concomitantly reduced SHP-2-PI3K-Akt2 signaling decrease osteoblast differentiation. Biochem Biophys Res Commun. 2016;478:268-273 pubmed publisher
    ..The cell surface glycoprotein CD47 and its receptor signal regulatory protein alpha (SIRP?) have both been suggested to regulate bone cell differentiation...
  71. Zhao J, Lurie D. Cochlear ablation in mice lacking SHP-1 results in an extended period of cell death of anteroventral cochlear nucleus neurons. Hear Res. 2004;189:63-75 pubmed
    ..These results indicate that activated microglia may participate in determining whether neurons in AVCN live or die following deafferentation. ..
  72. Ishikawa Sekigami T, Kaneko Y, Okazawa H, Tomizawa T, Okajo J, Saito Y, et al. SHPS-1 promotes the survival of circulating erythrocytes through inhibition of phagocytosis by splenic macrophages. Blood. 2006;107:341-8 pubmed
    ..These results suggest that SHPS-1 negatively regulates the phagocytosis of RBCs by splenic macrophages, thereby determining both the lifespan of individual RBCs and the number of circulating erythrocytes. ..
  73. Ishikawa Sekigami T, Kaneko Y, Saito Y, Murata Y, Okazawa H, Ohnishi H, et al. Enhanced phagocytosis of CD47-deficient red blood cells by splenic macrophages requires SHPS-1. Biochem Biophys Res Commun. 2006;343:1197-200 pubmed
    ..These results thus suggest an additional role for CD47 on RBCs in the negative regulation of phagocytosis by macrophages and in determination of the life span of circulating RBCs. ..