Platelet basic protein (PBP) is a protein that in humans is encoded by the gene PPBP (previously CXCL7). PBP is a precursor protein that is cleaved into multiple distinct active proteins, notable Connective tissue-activating peptide III (CTAP-III), Beta-thromboglobulin (Beta-TG), Neutrophil-activating peptide 2 (NAP-2), TC-1, and TC-2. PPBP is first translated into the precursor molecule pro-platelet basic protein (PPBP), the first 34 amino acids of which correspond to the signal peptide, while the remaining amino acid residues at positions 35-128 compose PBP.
Connective tissue-activating peptide III (CTAP-III), also called Low-affinity platelet factor IV (LA-PF4), is a protein that corresponds to positions 44-128 of PPBP. This protein has mitogenic effects: stimulating DNA synthesis and mitosis. It also triggers prostaglandin E2 secretion and synthesis of hyaluronic acid and sulfated glycosaminoglycan.
Neutrophil-activating peptide 2
Neutrophil-activating peptide 2 (NAP-2) is a chemokine that corresponds to positions 59-128 of PPBP. NAP-2 activates and attracts neutrophils through interaction with the receptors CXCR1 and CXCR2. There are also shorter (and longer) versions of this peptide with similar effects, with NAP-2(1-63) (corresponding to positions 59-121 of PPBP) being the most potent.
TC-1 and TC-2
TC-1 and TC-2 are antimicrobial proteins corresponding to positions 59-126 and 44-126 of the PPBP protein respectively.
β-TG also affects megakaryocyte maturation, and thus helps in regulating platelet production.
Clinical uses
Levels of β-TG is used to index platelet activation. It is measured by ELISA in blood plasma or urine, and often in conjunction with PF4.
Influences
β-TG levels may increase with age. It is elevated in diabetes mellitus.
β-TG levels have been found to be increased by treatment with the syntheticestrogenethinylestradiol, though were not significantly increased by the natural estrogen estradiol valerate. Levels of β-TG have also been found to be increased or unchanged during normal pregnancy.
↑Lindberg UB, Crona N, Stigendal L, Teger-Nilsson AC, Silfverstolpe G (February 1989). "A comparison between effects of estradiol valerate and low dose ethinyl estradiol on haemostasis parameters". Thromb Haemost. 61 (1): 65–9. doi:10.1055/s-0038-1646528. PMID2526387.
↑Hellgren M (April 2003). "Hemostasis during normal pregnancy and puerperium". Semin Thromb Hemost. 29 (2): 125–30. doi:10.1055/s-2003-38897. PMID12709915.
Further reading
Begg GS, Pepper DS, Chesterman CN, Morgan FJ (1978). "Complete covalent structure of human beta-thromboglobulin". Biochemistry. 17 (9): 1739–44. doi:10.1021/bi00602a024. PMID77677.
Cohen AB, Stevens MD, Miller EJ, etal. (1992). "Generation of the neutrophil-activating peptide-2 by cathepsin G and cathepsin G-treated human platelets". Am. J. Physiol. 263 (2 Pt 1): L249–56. doi:10.1152/ajplung.1992.263.2.L249. PMID1387511.
Morris SW, Nelson N, Valentine MB, etal. (1992). "Assignment of the genes encoding human interleukin-8 receptor types 1 and 2 and an interleukin-8 receptor pseudogene to chromosome 2q35". Genomics. 14 (3): 685–91. doi:10.1016/S0888-7543(05)80169-7. PMID1427896.
Wenger RH, Hameister H, Clemetson KJ (1991). "Human platelet basic protein/connective tissue activating peptide-III maps in a gene cluster on chromosome 4q12-q13 along with other genes of the beta-thromboglobulin superfamily". Hum. Genet. 87 (3): 367–8. doi:10.1007/BF00200921. PMID1830861. S2CID19420329.
Hjemdahl P, Perneby C, Theodorsson E, etal. (1992). "A new assay for beta-thromboglobulin in urine". Thromb. Res. 64 (1): 33–43. doi:10.1016/0049-3848(91)90203-9. PMID1837963.
Brandt E, Van Damme J, Flad HD (1991). "Neutrophils can generate their activator neutrophil-activating peptide 2 by proteolytic cleavage of platelet-derived connective tissue-activating peptide III". Cytokine. 3 (4): 311–21. doi:10.1016/1043-4666(91)90499-4. PMID1873479.
Clark-Lewis I, Moser B, Walz A, etal. (1991). "Chemical synthesis, purification, and characterization of two inflammatory proteins, neutrophil activating peptide 1 (interleukin-8) and neutrophil activating peptide". Biochemistry. 30 (12): 3128–35. doi:10.1021/bi00226a021. PMID2007144.
Holt JC, Harris ME, Holt AM, etal. (1986). "Characterization of human platelet basic protein, a precursor form of low-affinity platelet factor 4 and beta-thromboglobulin". Biochemistry. 25 (8): 1988–96. doi:10.1021/bi00356a023. PMID2423119.
Walz A, Baggiolini M (1989). "A novel cleavage product of beta-thromboglobulin formed in cultures of stimulated mononuclear cells activates human neutrophils". Biochem. Biophys. Res. Commun. 159 (3): 969–75. Bibcode:1989BBRC..159..969W. doi:10.1016/0006-291X(89)92203-1. PMID2522778.
Castor CW, Walz DA, Ragsdale CG, etal. (1989). "Connective tissue activation. XXXIII. Biologically active cleavage products of CTAP-III from human platelets". Biochem. Biophys. Res. Commun. 163 (2): 1071–8. Bibcode:1989BBRC..163.1071C. doi:10.1016/0006-291X(89)92330-9. PMID2783111.
Holt JC, Rabellino EM, Gewirtz AM, etal. (1988). "Occurrence of platelet basic protein, a precursor of low affinity platelet factor 4 and beta-thromboglobulin, in human platelets and megakaryocytes". Exp. Hematol. 16 (4): 302–6. PMID2966071.
Castor CW, Furlong AM, Carter-Su C (1985). "Connective tissue activation: stimulation of glucose transport by connective tissue activating peptide III". Biochemistry. 24 (7): 1762–7. doi:10.1021/bi00328a029. PMID4005226.