The 27-kDa heat shock protein facilitates basic fibroblast growth factor release from endothelial cells.
Basic fibroblast growth factor is an important mitogenic and angiogenic factor that stimulates endothelial cell growth and migration. This hormone is not secreted via the classical vesicular pathway, and the identification of intracellular proteins that facilitate its release remains lacking. Transfection and expression of the 27-kDa human heat shock protein in bovine arterial endothelial cells doubles the rate of estrogen-induced basic fibroblast growth factor secretion, preferentially inducing the release of high molecular weight forms of the hormone. The secreted basic fibroblast growth factor is mitogenic to breast adenocarcinoma cells cultured in the conditioned medium obtained from the transfected endothelial cells. In contrast, decreasing the level of the endogenous heat shock protein homolog with an antisense vector markedly decreases basic fibroblast growth factor release. Anti-heat shock protein or anti-basic fibroblast growth factor antibodies co-precipitate both proteins from endothelial cell extracts, demonstrating a direct association between the two proteins. This interaction is likely to be an important step in the mechanism of basic fibroblast growth factor secretion.
Piotrowicz
R S
RS
Department of Vascular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Martin
J L
JL
Dillman
W H
WH
Levin
E G
EG
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*
D006360:Heat-Shock Proteins; D011960:Receptors, Estrogen; D016222:Fibroblast Growth Factor 2