Summary of mouse platelet ITIM-containing receptors
| Receptor . | Characteristics . | Mouse models . | Signaling . | References . |
|---|---|---|---|---|
| PECAM-1 (CD31) | Expression: nonerythroid hematopoietic cells, endothelium | Constitutive KO | Attenuates ITAM, thrombin, and integrin receptor signaling | 17, 30, 36,,-39, 42, 44, 45, 47 |
| Isoforms: various, Δ15 most prevalent in human platelets | Platelet count: normal, delayed recovery after depletion | ↑ phosphorylation, Shp1 and Shp2 interaction to collagen, thrombin, fibrinogen, and anti–PECAM-1 antibody stimulation | ||
| MW: 130 kDa | Platelet volume: normal | |||
| Ectodomain: 6 IgC2-like domains, glycosylated | Receptor levels: normal | |||
| Ligands: trans homophilic, CD177, CD38, αvβ3 | Functional responses: ↑ collagen, thrombin aggregation | |||
| Intracellular motifs: palmitoylation (C594), PRR, ITIM (Y662), ITSM (Y685) | Integrin function: ↓ spreading on fibrinogen, ↓ clot retraction | |||
| Interactions: Shp1, Shp2, SHIP1, p85 (PI3K), Lyn | Hemostasis: ↑ tail bleeding | |||
| Thrombosis: ↑ onset, size, stability in laser and ferric chloride injury models | ||||
| G6b-B | Expression: megakaryocyte and platelet specific | Constitutive and Pf4-Cre KO | Attenuates GPVI- and ADP-induced aggregation and Ca2+ release | 56,,-59, 64 |
| Isoforms: membrane associated (-A and -B) and predicted secreted (-C, -D, and -E) | Platelet count: ↓ 77%, increased clearance and reduced production | ↑ basal Syk phosphorylation (pY519/20) in G6b−/− platelets | ||
| MW: 24-30kDa doublet, glycosylated | Platelet volume: ↑ 38% | Basally phosphorylated | ||
| Ectodomain: single IgV-like domain | Receptor levels: ↓ 80% GPVI, minor ↓ α2, GPIbα, and CLEC-2, ↑ ADAM-10 | ↑ phosphorylation, Shp1 and Shp2 interaction to CRP and thrombin | ||
| Ligands: heparin | Functional responses: ↓ GPVI aggregation, ↑ CLEC-2 aggregation, thrombin aggregation reversible | |||
| Intracellular motifs: PRR, ITIM (Y195), ITSM (Y221) | Integrin function: ↓ platelet spreading on fibrinogen with thrombin preactivation, ↓ megakaryocyte spreading on fibrinogen, fibronectin, and collagen | |||
| Interactions: Shp1, Shp2, (Syk, PLCγ2 – only by SPR), Fyn>Src | Hemostasis: ↑↑ tail bleeding | |||
| Thrombosis: unknown | ||||
| TLT-1 | Expression: megakaryocyte and platelet specific | Constitutive KO | Augments platelet aggregation to multiple agonists | 20, 75, 77, 78, 80 |
| Isoforms: sTLT-1 (shed extracellular domain) | Platelet count: ↓ 20% | Associates with ERM proteins, potentially linking fibrinogen to the cytoskeleton | ||
| MW: 38 kDa | Platelet volume: unknown | |||
| Ectodomain: single IgV-like domain | Receptor levels: unknown | |||
| Ligands: fibrinogen | Functional responses: ↓ ADP and U46619 aggregation, delayed collagen and thrombin aggregation | |||
| Intracellular motifs: palmitoylation (C188), PRR, ITIM (Y266) | Integrin function: ↓ fibrinogen binding with ADP stimulation | |||
| Interactions: Shp1, Shp2, ERM proteins | Thrombosis: unknown | |||
| Hemostasis: ↑ tail bleeding | ||||
| Other: ↑ systemic inflammatory response to LPS | ||||
| CEACAM1 (Bgp-1) | Expression: immune, hematologic, epithelial, and endothelial cells | Constitutive KO | Attenuates GPVI- and CLEC-2–mediated platelet activation, potentially via PLCγ2 | 21, 83 |
| Isoforms: most dominant is CEACAM1L-4L (4 denotes the number of IgG domains, L denotes the long intracellular domain that contains the ITIMs) | Platelet count: normal | Direct association and implicated in regulating function of αIIbβ3 | ||
| MW: 160 kDa, heavily glycosylated | Platelet volume: unknown | |||
| Ectodomain: 1 IgV-like domain and 3 IgC2-like domains | Receptor levels: normal | |||
| Ligands: homophilic | Functional responses: ↑ GPVI aggregation, granule release and flow adhesion | |||
| Intracellular motifs: ITIMs (Y454), ITSM (Y481), PRR | Integrin function: ↓ platelet spreading on fibrinogen, ↓ clot retraction | |||
| Interactions: Shp1, Shp2 | Hemostasis: ↑ tail bleeding | |||
| Thrombosis: form larger, more stable thrombi | ||||
| CEACAM2 (Bgp-2) | Expression: platelets, intestinal tissue crypt epithelia, kidney, testis, and several brain nuclei | Constitutive KO | Attenuates GPVI- and CLEC-2–mediated platelet activation | 22, 84 |
| Isoforms: most dominant in platelets is CEACAM2-2L | Platelet count: normal | Augmented phosphorylation of PLCγ2, Src, and Syk in response to CRP and rhodocytin in ceacam2−/− platelets | ||
| MW: 52 kDa, glycosylated | Platelet volume: unknown | |||
| Ectodomain: 1 IgV-like domain and 1 IgC2-like domain | Receptor levels: normal | |||
| Ligands: coronavirus mouse hepatitis virus spike GPs | Functional responses: ↑ GPVI aggregation, granule release and flow adhesion, ↑ CLEC-2 aggregation | |||
| Intracellular motifs: ITIM (Y273), PRR, ITSM (Y300) | Integrin function: ↓ platelet spreading on fibrinogen, ↓ clot retraction | |||
| Interactions: Shp1, Shp2 | Hemostasis: ↑ tail bleeding | |||
| Thrombosis: form larger, more stable thrombi | ||||
| PIR-B (LILRB2) | Expression: platelets, immune cells (monocytes, macrophages, and dendritic cells), hematopoietic cells, and neurons | Deletion of intracellular tail | Attenuates collagen-, thrombin-, and ADP-induced platelet activation | 23, 88 |
| Isoforms: 7 members | Platelet count: ↑ 47% | Attenuates Syk and FcRγ signaling on antibody-mediated cross-linking in immune cells | ||
| MW: 125 kDa, glycosylated | Platelet volume: unknown | ANGPLT2 attenuates GPVI-induced phosphorylation of LAT, SLP76, and PLCγ2 partially via PIR-B | ||
| Ectodomain: 6 IgC2-like domains, glycosylated | Receptor levels: unknown | |||
| Ligands: angiopoietin-like protein 2 (ANGPLT2) | Functional responses: ↑ GPVI aggregation and granule release, ↑ ADP and thrombin aggregation | |||
| Intracellular motifs: ITIM (Y770), PRR | Integrin function: ↑ platelet spreading on fibrinogen | |||
| Interactions: Shp1, Shp2 | Hemostasis: unknown | |||
| Thrombosis: unknown |
| Receptor . | Characteristics . | Mouse models . | Signaling . | References . |
|---|---|---|---|---|
| PECAM-1 (CD31) | Expression: nonerythroid hematopoietic cells, endothelium | Constitutive KO | Attenuates ITAM, thrombin, and integrin receptor signaling | 17, 30, 36,,-39, 42, 44, 45, 47 |
| Isoforms: various, Δ15 most prevalent in human platelets | Platelet count: normal, delayed recovery after depletion | ↑ phosphorylation, Shp1 and Shp2 interaction to collagen, thrombin, fibrinogen, and anti–PECAM-1 antibody stimulation | ||
| MW: 130 kDa | Platelet volume: normal | |||
| Ectodomain: 6 IgC2-like domains, glycosylated | Receptor levels: normal | |||
| Ligands: trans homophilic, CD177, CD38, αvβ3 | Functional responses: ↑ collagen, thrombin aggregation | |||
| Intracellular motifs: palmitoylation (C594), PRR, ITIM (Y662), ITSM (Y685) | Integrin function: ↓ spreading on fibrinogen, ↓ clot retraction | |||
| Interactions: Shp1, Shp2, SHIP1, p85 (PI3K), Lyn | Hemostasis: ↑ tail bleeding | |||
| Thrombosis: ↑ onset, size, stability in laser and ferric chloride injury models | ||||
| G6b-B | Expression: megakaryocyte and platelet specific | Constitutive and Pf4-Cre KO | Attenuates GPVI- and ADP-induced aggregation and Ca2+ release | 56,,-59, 64 |
| Isoforms: membrane associated (-A and -B) and predicted secreted (-C, -D, and -E) | Platelet count: ↓ 77%, increased clearance and reduced production | ↑ basal Syk phosphorylation (pY519/20) in G6b−/− platelets | ||
| MW: 24-30kDa doublet, glycosylated | Platelet volume: ↑ 38% | Basally phosphorylated | ||
| Ectodomain: single IgV-like domain | Receptor levels: ↓ 80% GPVI, minor ↓ α2, GPIbα, and CLEC-2, ↑ ADAM-10 | ↑ phosphorylation, Shp1 and Shp2 interaction to CRP and thrombin | ||
| Ligands: heparin | Functional responses: ↓ GPVI aggregation, ↑ CLEC-2 aggregation, thrombin aggregation reversible | |||
| Intracellular motifs: PRR, ITIM (Y195), ITSM (Y221) | Integrin function: ↓ platelet spreading on fibrinogen with thrombin preactivation, ↓ megakaryocyte spreading on fibrinogen, fibronectin, and collagen | |||
| Interactions: Shp1, Shp2, (Syk, PLCγ2 – only by SPR), Fyn>Src | Hemostasis: ↑↑ tail bleeding | |||
| Thrombosis: unknown | ||||
| TLT-1 | Expression: megakaryocyte and platelet specific | Constitutive KO | Augments platelet aggregation to multiple agonists | 20, 75, 77, 78, 80 |
| Isoforms: sTLT-1 (shed extracellular domain) | Platelet count: ↓ 20% | Associates with ERM proteins, potentially linking fibrinogen to the cytoskeleton | ||
| MW: 38 kDa | Platelet volume: unknown | |||
| Ectodomain: single IgV-like domain | Receptor levels: unknown | |||
| Ligands: fibrinogen | Functional responses: ↓ ADP and U46619 aggregation, delayed collagen and thrombin aggregation | |||
| Intracellular motifs: palmitoylation (C188), PRR, ITIM (Y266) | Integrin function: ↓ fibrinogen binding with ADP stimulation | |||
| Interactions: Shp1, Shp2, ERM proteins | Thrombosis: unknown | |||
| Hemostasis: ↑ tail bleeding | ||||
| Other: ↑ systemic inflammatory response to LPS | ||||
| CEACAM1 (Bgp-1) | Expression: immune, hematologic, epithelial, and endothelial cells | Constitutive KO | Attenuates GPVI- and CLEC-2–mediated platelet activation, potentially via PLCγ2 | 21, 83 |
| Isoforms: most dominant is CEACAM1L-4L (4 denotes the number of IgG domains, L denotes the long intracellular domain that contains the ITIMs) | Platelet count: normal | Direct association and implicated in regulating function of αIIbβ3 | ||
| MW: 160 kDa, heavily glycosylated | Platelet volume: unknown | |||
| Ectodomain: 1 IgV-like domain and 3 IgC2-like domains | Receptor levels: normal | |||
| Ligands: homophilic | Functional responses: ↑ GPVI aggregation, granule release and flow adhesion | |||
| Intracellular motifs: ITIMs (Y454), ITSM (Y481), PRR | Integrin function: ↓ platelet spreading on fibrinogen, ↓ clot retraction | |||
| Interactions: Shp1, Shp2 | Hemostasis: ↑ tail bleeding | |||
| Thrombosis: form larger, more stable thrombi | ||||
| CEACAM2 (Bgp-2) | Expression: platelets, intestinal tissue crypt epithelia, kidney, testis, and several brain nuclei | Constitutive KO | Attenuates GPVI- and CLEC-2–mediated platelet activation | 22, 84 |
| Isoforms: most dominant in platelets is CEACAM2-2L | Platelet count: normal | Augmented phosphorylation of PLCγ2, Src, and Syk in response to CRP and rhodocytin in ceacam2−/− platelets | ||
| MW: 52 kDa, glycosylated | Platelet volume: unknown | |||
| Ectodomain: 1 IgV-like domain and 1 IgC2-like domain | Receptor levels: normal | |||
| Ligands: coronavirus mouse hepatitis virus spike GPs | Functional responses: ↑ GPVI aggregation, granule release and flow adhesion, ↑ CLEC-2 aggregation | |||
| Intracellular motifs: ITIM (Y273), PRR, ITSM (Y300) | Integrin function: ↓ platelet spreading on fibrinogen, ↓ clot retraction | |||
| Interactions: Shp1, Shp2 | Hemostasis: ↑ tail bleeding | |||
| Thrombosis: form larger, more stable thrombi | ||||
| PIR-B (LILRB2) | Expression: platelets, immune cells (monocytes, macrophages, and dendritic cells), hematopoietic cells, and neurons | Deletion of intracellular tail | Attenuates collagen-, thrombin-, and ADP-induced platelet activation | 23, 88 |
| Isoforms: 7 members | Platelet count: ↑ 47% | Attenuates Syk and FcRγ signaling on antibody-mediated cross-linking in immune cells | ||
| MW: 125 kDa, glycosylated | Platelet volume: unknown | ANGPLT2 attenuates GPVI-induced phosphorylation of LAT, SLP76, and PLCγ2 partially via PIR-B | ||
| Ectodomain: 6 IgC2-like domains, glycosylated | Receptor levels: unknown | |||
| Ligands: angiopoietin-like protein 2 (ANGPLT2) | Functional responses: ↑ GPVI aggregation and granule release, ↑ ADP and thrombin aggregation | |||
| Intracellular motifs: ITIM (Y770), PRR | Integrin function: ↑ platelet spreading on fibrinogen | |||
| Interactions: Shp1, Shp2 | Hemostasis: unknown | |||
| Thrombosis: unknown |
Residues are numbered according to the mature mouse protein after cleavage of the signal peptide.
MW, molecular weight (western blotting); Pf4-Cre, platelet factor 4 promotor driven Cre-recombinase transgenic mouse.