ISSN:
0730-2312
Keywords:
growth factor
;
macrophage
;
peptide synthesis
;
thrombin
;
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
It has been recognized for many years that α-thrombin, like other better known mitogens (eg, PDGF, EOF, etc) is capable of initiating proliferation in quiescent cells belonging to the fibroblast family. However, unlike these other peptides, thrombin is a serine protease whose function as a growth stimulator for fibroblasts is intimately linked to its estefolytic activity. Thus, while native α-thrombin is capable of evoking DNA synthesis in GoG1-arrested cells, neither enzymatically inactive thrombin (eg, iPR2P-α-thrombin) nor partially degraded thrombin (eg, γ-thrombin) shares in this capability. Data from our laboratory have shown that thrombin is chemotactic for peripheral blood monocytes and for cells belonging to the monocyte/macrophage family and that this activity is not dependent upon thrombin's enzymatic properties. Our recent findings demonstrate that thrombin also serves as a growth factor for these cells, and this mitogenic capability is independent of esterolytic function and resides in the same region of the molecule as that responsible for chemotaxis. Additionally, by means of techniques such as computer modeling and peptide synthesis, we have now been able to delineate a distinct mitogenic subsite within this chemotactic thrombin sequence. Thus, the sequence in the thrombin B chain that mediates chemotaxis represents a true cell interactive exosite additionally capable of stimulating growth and possibly other biological functions in cells of macrophage/monocyte lineage.
Additional Material:
5 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jcb.240320403
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