Independent effects of platelet-derived growth factor isoforms on mitogen-activated protein kinase activation and mitogenesis in human dermal fibroblasts
Mitogen-activated protein kinase (MAPK) is activated in many cell types in response to growth factors during the G0-G1 transition in the cell cycle. We investigated the effects of platelet-derived growth factor (PDGF) AA and PDGF BB on activation of MAPK in human dermal fibroblasts, and asked whethe...
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Published in | The Journal of biological chemistry Vol. 269; no. 13; pp. 9822 - 9825 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Bethesda, MD
American Society for Biochemistry and Molecular Biology
01.04.1994
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Subjects | |
Online Access | Get full text |
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Summary: | Mitogen-activated protein kinase (MAPK) is activated in many cell types in response to growth factors during the G0-G1 transition
in the cell cycle. We investigated the effects of platelet-derived growth factor (PDGF) AA and PDGF BB on activation of MAPK
in human dermal fibroblasts, and asked whether its activation correlates with proliferative responses of human fibroblasts
to PDGF AA and PDGF BB. Treatment with either PDGF isoform for 20 min resulted in equal phosphorylation of MAPK as visualized
by gel shifts in Western blotting with anti-MAPK polyclonal antibody. This finding was confirmed by measurements of MAPK activity
in response to increasing doses (2-20 ng/ml) of PDGF AA and PDGF BB in in vitro assays with myelin basic protein as a substrate.
PDGF AA was slightly less potent than PDGF BB, but both growth factors induced similar maximal activations. Kinetics of activation
were also similar for both isoforms, with maximal induction of MAPK at 10-20 min after growth factor addition followed by
a gradual decline to control levels at 1 h. Activation of MAPK by both PDGF isoforms was also confirmed by measuring myelin
basis protein phosphorylation in MAPK immunoprecipitates. Thus both PDGF AA and PDGF BB are potent activators of MAPK in human
dermal fibroblasts. In contrast, PDGF BB elicited a strong mitogenic response, while PDGF AA had no significant effect on
DNA synthesis in human dermal fibroblasts. These data indicate that acute activation of MAPK is not sufficient to stimulate
cells to progress through cell cycle. PDGF AA may have other biologic functions or may play a co-stimulatory role in proliferation
of human dermal fibroblasts. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/S0021-9258(17)36957-0 |