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Early signals in the mitogenic response of Swiss 3T3 cells: a comparative study of purified PDGF homodimers
Imperial Cancer Research Fund Laboratories, London, United Kingdom.
Imperial Cancer Research Fund Laboratories, London, United Kingdom; Department of Pathology, University Hospital, Uppsala, Sweden.ORCID iD: 0000-0001-8889-5803
Imperial Cancer Research Fund Laboratories, London, United Kingdom.
ZymoGenetics Inc., Seattle, Washington.
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1990 (English)In: Growth Factors, ISSN 0897-7194, E-ISSN 1029-2292, Vol. 3, no 2, p. 83-95Article in journal (Refereed) Published
Abstract [en]

Platelet-derived growth factor (PDGF) occurs as three dimeric isoforms, AA, BB, and AB. Two distinct receptor subunits, alpha and beta, have been identified which bind either all three isoforms of PDGF (alpha) or PDGF-BB only (beta). Here, we have compared the effect of purified PDGF homodimers on the early intracellular signaling events and mitogenesis in Swiss 3T3 cells, which possess equivalent numbers of the alpha and beta subunits. Both PDGF-AA and PDGF-BB stimulated receptor phosphorylation, inositol phosphate formation, activation of protein kinase C, calcium mobilization, EGF receptor transmodulation, sodium uptake, arachidonic acid release, cyclic AMP accumulation, and c-fos induction in a comparable, dose-dependent manner (half-maximal values for all these response were in the 2-10 ng/ml range for both homodimers). At high concentrations of PDGF (greater than 10 ng/ml), the BB homodimer effect on early membrane and cytosolic signals was 20-30% greater than PDGF-AA, reflecting the greater number of available binding sites for PDGF-BB. DNA synthesis studies indicated that PDGF-AA and PDGF-BB were potent mitogens for Swiss 3T3 cells, displaying identical dose-response effects. Moreover, the mitogenic activities of both homodimers were equally potentiated in the presence of insulin. These results indicate that both PDGF-AA and PDGF-BB stimulate the full complement of molecular responses required for the synergistic interactions mediating long-term mitogenesis. We conclude that alpha and beta receptor subunits do not differ in their ability to transduce PDGF-mediated signals leading to DNA synthesis in Swiss 3T3 cells.

Place, publisher, year, edition, pages
Taylor & Francis, 1990. Vol. 3, no 2, p. 83-95
Keywords [en]
tyrosine kinase, protein kinase C, calcium, inositol phosphate, arachidonic acid, cyclic AMP, c-fos, c-myc
National Category
Medical and Health Sciences Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:oru:diva-79039DOI: 10.3109/08977199009108271ISI: 000497575300001PubMedID: 2169773Scopus ID: 2-s2.0-0025651050OAI: oai:DiVA.org:oru-79039DiVA, id: diva2:1386325
Available from: 2013-10-21 Created: 2020-01-17 Last updated: 2020-01-27Bibliographically approved

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