Early Signals in the Mitogenic Response of Swiss 3T3 Cells: A Comparative Study of Purified PDGF Homodimers
作者:
MehmetHuseyin,
NånbergEewa,
LehmannWolfram,
MurrayMark J.,
RozengurtEnrique,
期刊:
Growth Factors
(Taylor Available online 1990)
卷期:
Volume 3,
issue 2
页码: 83-95
ISSN:0897-7194
年代: 1990
DOI:10.3109/08977199009108271
出版商: Taylor&Francis
关键词: tyrosine kinase;protein kinase C;calcium;inositol phosphate;arachidonic acid;cyclic AMP;c-fos;c-myc
数据来源: Taylor
摘要:
AbstractPlatelet-derived growth factor (PDGF) occurs as three dimeric isoforms, AA, BB, and AB. Two distinct receptor subunits,αandβ, have been identified which bind either all three isoforms of PDGF (α) or PDGF-BB only (β). 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 theαandβsubunits. 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, andc-fosinduction in a comparable, dose-dependent manner (half-maximal values for all these responses were in the 2–10 ng/ml range for both homodimers). At high concentrations of PDGF (>10 ng/ml), the BB homo-dimer 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 thatαandβreceptor subunits do not differ in their ability to transduce PDGF-mediated signals leading to DNA synthesis in Swiss 3T3 cells.
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