Open AccessCleavage of the membrane precursor for transforming growth factor alpha is a regulated process.
Author(s) -
Atanasio Pandiella,
Joan Massagué
Publication year - 1991
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.88.5.1726
Subject(s) - cleavage (geology) , cleavage stimulation factor , juxtacrine signalling , microbiology and biotechnology , growth factor , tgf alpha , cell membrane , chemistry , protein kinase c , paracrine signalling , cell , biology , biochemistry , cleavage factor , signal transduction , receptor , paleontology , fracture (geology) , messenger rna , gene
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.