Platelet factor 4 Information & Platelet factor 4 Links at HealthHaven.com

Platelet factor 4 (chemokine (C-X-C motif) ligand 4)
	PDB rendering based on 1f9q.
Available structures
	1f9q, 1f9r, 1f9s, 1pfm, 1pfn, 1rhp
Identifiers
Symbols	PF4; CXCL4; MGC138298; SCYB4
External IDs	OMIM: 173460 MGI: 1888711 HomoloGene: 87791
Gene ontology
Molecular function	• chemokine activity; • heparin binding;
Cellular component	• extracellular region; • extracellular space;
Biological process	• immune response; • negative regulation of angiogenesis; • cytokine and chemokine mediated signaling pathway; • platelet activation; • leukocyte chemotaxis; • negative regulation of megakaryocyte differentiation;
RNA expression pattern
	More reference expression data
Orthologs
NP_002610 (protein)	NP_064316 (protein)

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Platelet factor 4 (PF4) is a small cytokine belonging to the CXC chemokine family that is also known as chemokine (C-X-C motif) ligand 4 (CXCL4) . This chemokine is released from alpha-granules of activated platelets during platelet aggregation, and promotes blood coagulation by moderating the effects of heparin-like molecules. Due to these roles, it is predicted to play a role in wound repair and inflammation.^[1] It is usually found in a complex with proteoglycan.

PF4 is chemotactic for neutrophils, fibroblasts and monocytes, and interacts with a splice variant of the chemokine receptor CXCR3, known as CXCR3B.^[2] The gene for human PF4 is located on human chromosome 4.^[3]

Platelet factor-4 is a 70-amino acid protein that is released from the alpha-granules of activated platelets and binds with high affinity to heparin. Its major physiologic role appears to be neutralization of heparin-like molecules on the endothelial surface of blood vessels, thereby inhibiting local antithrombin III activity and promoting coagulation. As a strong chemoattractant for neutrophils and fibroblasts, PF4 probably has a role in inflammation and wound repair (Eisman et al., 1990).[supplied by OMIM]^[4]

PF4 is the antigen in heparin-induced thrombocytopenia, an idiosyncratic autoimmune reaction to the administration of the anticoagulant heparin.^[5] PF4 autoantibodies have also been found in patients with thrombosis and features resembling HIT but no prior administration of heparin.^[6]

[edit] References

^ Eisman R, Surrey S, Ramachandran B, Schwartz E, Poncz M (1990). "Structural and functional comparison of the genes for human platelet factor 4 and PF4alt". Blood 76 (2): 336–44. PMID 1695112.
^ Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, Cosmi L, Sagrinati C, Mazzinghi B, Orlando C, Maggi E, Marra F, Romagnani S, Serio M, Romagnani P (2003). "An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4". J Exp Med 197 (11): 1537–49. doi:10.1084/jem.20021897. PMID 12782716.
^ O'Donovan N, Galvin M, Morgan J (1999). "Physical mapping of the CXC chemokine locus on human chromosome 4". Cytogenet Cell Genet 84 (1-2): 39–42. doi:10.1159/000015209. PMID 10343098.
^ "Entrez Gene: PF4 platelet factor 4 (chemokine (C-X-C motif) ligand 4)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5196.
^ Warkentin TE (March 2007). "Drug-induced immune-mediated thrombocytopenia--from purpura to thrombosis". N. Engl. J. Med. 356 (9): 891–3. doi:10.1056/NEJMp068309. PMID 17329695. http://content.nejm.org/cgi/content/full/356/9/891.
^ Warkentin TE, Makris M, Jay RM, Kelton JG (July 2008). "A spontaneous prothrombotic disorder resembling heparin-induced thrombocytopenia". Am. J. Med. 121 (7): 632–6. doi:10.1016/j.amjmed.2008.03.012. PMID 18589060.

[edit] Further reading

Bikfalvi A, Gimenez-Gallego G (2004). "The control of angiogenesis and tumor invasion by platelet factor-4 and platelet factor-4-derived molecules.". Semin. Thromb. Hemost. 30 (1): 137–44. doi:10.1055/s-2004-822978. PMID 15034805.
Maurer AM, Zhou B, Han ZC (2007). "Roles of platelet factor 4 in hematopoiesis and angiogenesis.". Growth Factors 24 (4): 242–52. PMID 17381065.
Deuel TF, Keim PS, Farmer M, Heinrikson RL (1977). "Amino acid sequence of human platelet factor 4.". Proc. Natl. Acad. Sci. U.S.A. 74 (6): 2256–8. PMID 267922.
Walz DA, Wu VY, de Lamo R, et al. (1978). "Primary structure of human platelet factor 4.". Thromb. Res. 11 (6): 893–8. PMID 601757.
Nath N, Lowery CT, Niewiarowski S (1975). "Antigenic and antiheparin properties of human platelet factor 4 (PF4).". Blood 45 (4): 537–50. PMID 803847.
Hermodson M, Schmer G, Kurachi K (1977). "Isolation, crystallization, and primary amino acid sequence of human platelet factor 4.". J. Biol. Chem. 252 (18): 6276–9. PMID 893407.
Maione TE, Gray GS, Petro J, et al. (1990). "Inhibition of angiogenesis by recombinant human platelet factor-4 and related peptides.". Science 247 (4938): 77–9. PMID 1688470.
Eisman R, Surrey S, Ramachandran B, et al. (1990). "Structural and functional comparison of the genes for human platelet factor 4 and PF4alt.". Blood 76 (2): 336–44. PMID 1695112.
Han ZC, Bellucci S, Tenza D, Caen JP (1990). "Negative regulation of human megakaryocytopoiesis by human platelet factor 4 and beta thromboglobulin: comparative analysis in bone marrow cultures from normal individuals and patients with essential thrombocythaemia and immune thrombocytopenic purpura.". Br. J. Haematol. 74 (4): 395–401. PMID 2140694.
Poncz M, Surrey S, LaRocco P, et al. (1987). "Cloning and characterization of platelet factor 4 cDNA derived from a human erythroleukemic cell line.". Blood 69 (1): 219–23. PMID 3098319.
Griffin CA, Emanuel BS, LaRocco P, et al. (1987). "Human platelet factor 4 gene is mapped to 4q12----q21.". Cytogenet. Cell Genet. 45 (2): 67–9. PMID 3622011.
Senior RM, Griffin GL, Huang JS, et al. (1983). "Chemotactic activity of platelet alpha granule proteins for fibroblasts.". J. Cell Biol. 96 (2): 382–5. PMID 6187750.
Morgan FJ, Begg GS, Chesterman CN (1980). "Complete covalent structure of human platelet factor 4.". Thromb. Haemost. 42 (5): 1652–60. PMID 6445090.
Deuel TF, Senior RM, Chang D, et al. (1981). "Platelet factor 4 is chemotactic for neutrophils and monocytes.". Proc. Natl. Acad. Sci. U.S.A. 78 (7): 4584–7. PMID 6945600.
Brown KJ, Parish CR (1994). "Histidine-rich glycoprotein and platelet factor 4 mask heparan sulfate proteoglycans recognized by acidic and basic fibroblast growth factor.". Biochemistry 33 (46): 13918–27. PMID 7524669.
Mayo KH, Roongta V, Ilyina E, et al. (1995). "NMR solution structure of the 32-kDa platelet factor 4 ELR-motif N-terminal chimera: a symmetric tetramer.". Biochemistry 34 (36): 11399–409. PMID 7547867.
Barker S, Mayo KH (1995). "Quarternary structure amplification of protein folding differences observed in 'native' platelet factor-4.". FEBS Lett. 357 (3): 301–4. PMID 7835432.
Zhang X, Chen L, Bancroft DP, et al. (1994). "Crystal structure of recombinant human platelet factor 4.". Biochemistry 33 (27): 8361–6. PMID 8031770.
Horne MK (1993). "The effect of secreted heparin-binding proteins on heparin binding to platelets.". Thromb. Res. 70 (1): 91–8. PMID 8511754.
Kolset SO, Mann DM, Uhlin-Hansen L, et al. (1996). "Serglycin-binding proteins in activated macrophages and platelets.". J. Leukoc. Biol. 59 (4): 545–54. PMID 8613703.