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. 1989 Oct;86(20):8063–8067. doi: 10.1073/pnas.86.20.8063

Autocrine mechanism for v-sis transformation requires cell surface localization of internally activated growth factor receptors.

T P Fleming 1, T Matsui 1, C J Molloy 1, K C Robbins 1, S A Aaronson 1
PMCID: PMC298215  PMID: 2813378

Abstract

v-sis represents a prototype for the class of oncogenes that encode growth factors. Whether its platelet-derived growth factor (PDGF)-like product functionally activates its receptors within the cell or at the cell surface has potential implications in efforts to intervene with the v-sis-transformed phenotype. We demonstrate that intracellular as well as cell surface forms of two PDGF receptor gene products are tyrosine phosphorylated in v-sis transformants. In a chemically defined medium in which cell growth was dependent on v-sis expression, proliferation was partially inhibited by PDGF neutralizing antibody but completely blocked by suramin. Suramin treatment resulted in a marked reduction in tyrosine phosphorylated cell surface PDGF receptors but had no effect on the level of tyrosine phosphorylation of intracellular receptor species. All of these findings demonstrate that the v-sis-encoded mitogen can bind and activate its receptors internally but that activated receptors must achieve a cell surface location in order to functionally couple with intracellular mitogenic signaling pathways.

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