Previously we have demonstrated that the phosphoinositide 3-kinase (PI-3K) signal-transduction pathway mediates platelet-derived growth factor (PDGF)-BB-induced glycosaminoglycan (GAG) synthesis in fetal lung fibroblasts. In the present study we further investigated the signal-transduction pathway(s) that results in PDGF-BB-induced GAG synthesis. Over-expression of a soluble PDGF β-receptor as well as a mutated form of the β-receptor, unable to bind PI-3K, diminished GAG synthesis in fetal lung fibroblasts subsequent to PDGF-BB stimulation. The PI-3K inhibitor wortmannin blocked PDGF-BB-induced Akt activity as well as significantly diminishing PDGF-BB-mediated GAG synthesis. Expression of dominant-negative PI-3K also abrogated Akt activity and GAG synthesis. Furthermore, expression of dominant-negative Akt abrogated endogenous Akt activity, Rab3D phosphorylation and GAG synthesis, whereas expression of constitutively activated Akt stimulated Rab3D phosphorylation and GAG synthesis in the absence of PDGF-BB. Over-expression of wild-type PTEN (phosphatase and tensin homologue deleted in chromosome 10) inhibited Akt activity and concomitantly attenuated GAG synthesis in fibroblasts stimulated with PDGF-BB. These data suggest that Akt is an integral protein involved in PDGF-BB-mediated GAG regulation in fetal lung fibroblasts.
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April 2002
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Research Article|
March 22 2002
Platelet-derived growth factor-BB-mediated glycosaminoglycan synthesis is transduced through Akt
Nicholas J. CARTEL;
Nicholas J. CARTEL
∗Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada M5G 1L5
†Canadian Institutes of Health Research Group in Lung Development, Programme in Lung Biology, Research Institute, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8
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Jinxia WANG;
Jinxia WANG
†Canadian Institutes of Health Research Group in Lung Development, Programme in Lung Biology, Research Institute, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8
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Martin POST
Martin POST
1
∗Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada M5G 1L5
†Canadian Institutes of Health Research Group in Lung Development, Programme in Lung Biology, Research Institute, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8
‡Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8
1To whom correspondence should be addressed, at the Canadian Institutes of Health Research Group in Lung Development, Hospital for Sick Children (e-mail martin.post@sickkids.on.ca).
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Biochem J (2002) 363 (1): 19–28.
Article history
Received:
October 09 2001
Revision Received:
December 06 2001
Accepted:
January 17 2002
Citation
Nicholas J. CARTEL, Jinxia WANG, Martin POST; Platelet-derived growth factor-BB-mediated glycosaminoglycan synthesis is transduced through Akt. Biochem J 1 April 2002; 363 (1): 19–28. doi: https://doi.org/10.1042/bj3630019
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