The TGF-α precursor expressed on the cell surface binds to the EGF receptor on adjacent cells, leading to signal transduction

Sharon T. Wong, Lisa F. Winchell, Bryan K. McCune, H. Shelton Earp, Joaquin Teixido, Joan Massague, Brian Herman, David C. Lee

Research output: Contribution to journalArticlepeer-review

362 Scopus citations

Abstract

The 50 amino acid form of TGF-α is cleaved from a conserved integral membrane glycoprotein by a protease that, in many tumor cells, appears to be limiting. To test whether the membrane-bound precursor has biological activity in the absence of processing, we introduced amino acid substitutions at the proteolytic cleavage sites. BHK cells transfected with expression vectors containing these altered sequences do not secrete detectable levels of mature TGF-α into the medium, but express high levels of proTGF-α at the cell surface. Coincubation of these BHK cells with A431 cells demonstrates that membrane-bound proTGF-α may bind to EGF receptors on the surface of contiguous cells, induce receptor autophosphorylation, and thereby produce a rapid rise in A431 intracellular calcium levels. Thus, proTGF-α can be biologically active in the absence of processing, a fact that may have implications for the integral membrane precursors of related growth factors.

Original languageEnglish (US)
Pages (from-to)495-506
Number of pages12
JournalCell
Volume56
Issue number3
DOIs
StatePublished - Feb 10 1989

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