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

T. P. Fleming, T. Matsui, C. J. Molloy, K. C. Robbins, S. A. Aaronson

Research output: Contribution to journalArticle

81 Citations (Scopus)

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 twp 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 of 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.

Original languageEnglish (US)
Pages (from-to)8063-8067
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume86
Issue number20
DOIs
StatePublished - Jan 1 1989

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Growth Factor Receptors
Tyrosine
Platelet-Derived Growth Factor Receptors
Suramin
Platelet-Derived Growth Factor
Neutralizing Antibodies
Mitogens
Oncogenes
Intercellular Signaling Peptides and Proteins
Phosphorylation
Phenotype
Growth
Genes

All Science Journal Classification (ASJC) codes

  • General

Cite this

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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 twp 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 of 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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Autocrine mechanism for v-sis transformation requires cell surface localization of internally activated growth factor receptors. / Fleming, T. P.; Matsui, T.; Molloy, C. J.; Robbins, K. C.; Aaronson, S. A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 86, No. 20, 01.01.1989, p. 8063-8067.

Research output: Contribution to journalArticle

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