The reference OMIM entry for this protein is 173460

Platelet factor 4; pf4
Small inducible cytokine subfamily b, member 4; scyb4
Chemokine, cxc motif, ligand 4; cxcl4

DESCRIPTION

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).

CLONING

The full-length PF4 cDNA was prepared by Poncz et al. (1987). Eisman et al. (1990) cloned and sequenced the PF4 gene. Like beta-thromboglobulin (PPBP; 121010), PF4 is encoded by a small inducible gene (SIG), so called because of its small size and its stimulation with platelet activation. The NOA mouse, an animal model of allergic or atopic dermatitis, exhibits ulcerative skin lesions associated with accumulation of mast cells and eosinophils, a significantly increased level of serum IgE, and scratching behavior. Watanabe et al. (1999) used the differential display technique to screen genes that might be differentially expressed in the spleen of NOA mice as compared to that of controls. They isolated a gene encoding a 105-amino acid protein that has 89% and 64% sequence identity to rat PF4 and human PF4, respectively. Both PF4 and eotaxin (601156), a specific chemoattractant for eosinophils, were expressed more strongly in spleens of adult NOA mice than in younger mice, parallel to the increase in ulcerative skin lesions in older mice. This suggested that PF4 and eotaxin may play important roles in the etiology of atopic dermatitis.

GENE FAMILY

PF4, or CXCL4, belongs to the CXC chemokine family. Chemokines are a group of small (approximately 8-14 kD), mostly basic, structurally related molecules that regulate cell trafficking of various types of leukocytes through interactions with a subset of 7-transmembrane, G protein-coupled receptors. Chemokines also play fundamental roles in the development, homeostasis, and function of the immune system, and they have effects on cells of the central nervous system as well as on endothelial cells involved in angiogenesis or angiostasis. Chemokines are divided into 2 major subfamilies, CXC and CC, based on the arrangement of the first 2 of the 4 conserved cysteine residues; the 2 cysteines are separated by a single amino acid in CXC chemokines and are adjacent in CC chemokines. CXC chemokines are further subdivided into ELR and non-ELR types based on the presence or absence of a glu-leu-arg sequence adjacent and N terminal to the CXC motif (summary by Strieter et al., 1995; Zlotnik and Yoshie, 2000).

GENE FUNCTION

Lasagni et al. (2003) identified an isoform of CXCR3 (300574), CXCR3B, as a functional receptor for CXCL4. The found that both CXCR3A and CXCR3B bound CXCL9 (601704), CXCL10 (147310), and CXCL11 (604852), but only CXCR3B bound CXCL4, following expression in a microvascular endothelial cell line. Overexpression of CXCR3A induced an increase in endothelial cell survival, whereas overexpression of CXCR3B upregulated apoptotic pathways. Immunohistochemical analysis of primary microvascular endothelial cells, whose growth in inhibited by CXCL4, CXCL9, CXCL10, and CXCL11, demonstrated expression of CXCR3B, but not CXCR3A. CXCR3B-specific monoclonal antibodies reacted with neoplastic tissue endothelial cells, providing evidence that CXCR3B is expr ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 173460 was added.

Feb. 23, 2019: Protein entry updated
Automatic update: comparative model was added.

Feb. 23, 2019: Protein entry updated
Automatic update: model status changed

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).