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Pro-Platelet basic protein (abbr. PPBP).
Beta-Thromboglobulin is stored in the Alpha-granules of platelets and released in large amounts after platelet activation.
Beta-Thromboglobulin is a protein of 8.85 kDa. It is synthesized in the cells as a biologically inactive 15 kDa precursor called PBP (platelet basic protein).
Removal of the nine aminoterminal amino acids from PBP by proteolytic cleavage yields a protein known as CTAP-3 (Connective tissue activating protein-3) or LA-PF4 (low affinity platelet factor-4). Removal of three amino acids from the aminoterminus of CTAP-3 yields Beta-Thromboglobulin.
CTAP-3 is the predominant form of the protein in platelets. The removal of 11 aminoterminal amino acids from Beta-Thromboglobulin by Cathepsin G yields another protein with neutrophil-activating activities, known as NAP-2 (neutrophil-activating protein-2).
The human gene encoding PBP, CTAP-3, and Beta-Thromboglobulin maps to chromosome 4q12-q13. It comprises three introns and has a length of 1.139 kb. A gene duplication of the Beta-Thromboglobulin gene, designated Beta-TG2, has been described.
The Beta-Thromboglobulin gene (SCYB7) is in close proximity (approximately 7 kb) of the gene encoding PF4 (platelet factor-4). The Beta-Thromboglobulin gene has been mapped to a region containing several genes encoding proteins belonging to the family of chemotactic cytokines known as Chemokines. The genes encoding IL8, MGSA (Melanoma growth stimulatory activity) and Beta-Thromboglobulin are located within a stretch of 700 kb.
Southern blot analysis of genomic DNA suggests that there are at least two copies of the Beta-Thromboglobulin gene, designated TGB1 and TGB2, in the human genome closely situated to each other. Only one gene (TGB1) has been shown to be expressed specifically in megakaryocytes.
Similarities of the protein sequences of Beta-Thromboglobulin and its precursor demonstrate that Beta-Thromboglobulin belongs to the family of chemotactic cytokines known as Chemokines (subroup of CXC-Chemokines).
Beta-Thromboglobulin is a strong chemoattractant for fibroblasts and is weakly chemotactic for neutrophils (see also: Chemotaxis). It stimulates mitogenesis, extracellular matrix synthesis, glucose metabolism, and plasminogen activator synthesis in cultures of human fibroblasts.
Beta-Thromboglobulin, its precursor, and its cleavage products influence the functional activities of neutrophilic granulocytes. Beta-Thromboglobulin affects the maturation of human megakaryocytes (see also: hematopoiesis) and thus could play a role in the physiological regulation of platelet production by megakaryocytes.
DETECTION AND ASSAY METHODS
Beta-Thromboglobulin is assayed by ELISA and other immunological tests. For further information on assays for cytokines see also: bioassays, cytokine assays.
CLINICAL USE AND SIGNIFICANCE
Serum plasma levels of Beta-Thromboglobulin (often in conjunction with PF4) and also concentrations of Beta-Thromboglobulin in urine are used as an index of platelet activation in a variety of clinical settings.
See REFERENCES for entry Beta-Thromboglobulin.
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