Pandiella A, Massagué J
Cell Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1726-30. doi: 10.1073/pnas.88.5.1726.
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.
转化生长因子α（TGF-α）是由膜锚定前体蛋白proTGF-α裂解产生的。proTGF-α以缓慢的速率裂解并积聚在细胞表面，从而介导细胞间黏附和有丝分裂刺激。我们在此表明，一种类弹性蛋白酶对膜proTGF-α的裂解是可溶性TGF-α生成过程中的一个重要调节步骤。裂解在血清因子和促肿瘤佛波酯的作用下被激活，导致细胞表面proTGF-α耗竭，其以可溶性因子的形式分散。proTGF-α裂解的激活由蛋白激酶C依赖性和非依赖性机制介导。这些结果证明了存在控制TGF-α从旁分泌生长因子向自分泌生长因子转换的机制。
