CLEAVAGE OF THE MEMBRANE PRECURSOR FOR TRANSFORMING GROWTH FACTOR-ALPHA IS A REGULATED PROCESS

被引:203
作者
PANDIELLA, A
MASSAGUE, J
机构
[1] MEM SLOAN KETTERING CANC CTR,CELL BIOL & GENET PROGRAM,NEW YORK,NY 10021
[2] MEM SLOAN KETTERING CANC CTR,HOWARD HUGES MED INST,NEW YORK,NY 10021
关键词
GROWTH FACTORS; MEMBRANE PROTEASES; PHORBOL ESTERS; PROHORMONES;
D O I
10.1073/pnas.88.5.1726
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Transforming growth factor-alpha (TGF-alpha) is generated by cleavage of a membrane-anchored precursor protein, proTGF-alpha. ProTGF-alpha is cleaved at a slow rate and accumulates on the cell surface, thereby mediating cell-cell adhesion and mitogenic stimulation. We show here that cleavage of membrane proTGF-alpha by an elastase-like enzyme constitutes an important regulatory step in the generation of soluble TGF-alpha. Cleavage is activated in response to serum factors and tumor-promoting phorbol esters, leading to depletion of cell surface proTGF-alpha, which disperses as soluble factor. Activation of proTGF-alpha cleavage is mediated by protein kinase C-dependent and -independent mechanisms. The results demonstrate the existence of mechanisms that control the switch of TGF-alpha from a juxtacrine to a paracrine growth factor.
引用
收藏
页码:1726 / 1730
页数:5
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