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Platelet-derived growth factor-BB-mediated glycosaminoglycan synthesis is transduced through Akt.

Authors: Cartel, NJ  Wang, J  Post, M 
Citation: Cartel NJ, etal., Biochem J. 2002 Apr 1;363(Pt 1):19-28.
Pubmed: (View Article at PubMed) PMID:11903042

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 beta-receptor as well as a mutated form of the beta-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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CRRD Object Information
CRRD ID: 1581762
Created: 2006-10-24
Species: All species
Last Modified: 2006-10-24
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.