Cleavage of the membrane precursor for transforming growth factor alpha is a regulated process.

Abstract:

: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.

authors

Pandiella A,Massagué J

doi

10.1073/pnas.88.5.1726

subject

Has Abstract

pub_date

1991-03-01 00:00:00

pages

1726-30

issue

5

eissn

0027-8424

issn

1091-6490

journal_volume

88

pub_type

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