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

2002 ◽  
Vol 363 (1) ◽  
pp. 19-28 ◽  
Author(s):  
Nicholas J. CARTEL ◽  
Jinxia WANG ◽  
Martin POST
Keyword(s):  
Signal Transduction ◽  
Growth Factor ◽  
Signal Transduction Pathway ◽  
Fetal Lung ◽  
Dominant Negative ◽  
Platelet Derived Growth Factor ◽  
Lung Fibroblasts ◽  
Transduction Pathway ◽  
Over Expression ◽  
Β Receptor

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.

scholarly journals BALB/c-3T3 fibroblasts resistant to growth inhibition by beta interferon exhibit aberrant platelet-derived growth factor, epidermal growth factor, and fibroblast growth factor signal transduction.

1991 ◽  
Vol 11 (6) ◽  
pp. 3148-3154 ◽  
Author(s):  
L J Mundschau ◽  
D V Faller
Keyword(s):  
Signal Transduction ◽  
Growth Factors ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Signal Transduction Pathway ◽  
Platelet Derived Growth Factor ◽  
Fibroblast Growth ◽  
Transduction Pathway ◽  
Double Stranded Rna ◽  
Epidermal Growth

Several lines of evidence now exist to suggest an interaction between the platelet-derived growth factor (PDGF) growth-stimulatory signal transduction pathway and the beta interferon (IFN-beta) growth-inhibitory signal transduction pathway. The most direct examples are inhibition of PDGF-mediated gene induction and mitogenesis by IFN-beta and the effects of activators and inhibitors of the IFN-inducible double-stranded RNA-dependent eIF2 kinase on expression of PDGF-inducible genes. To further investigate the nature of this PDGF/IFN-beta interaction, we selected BALB/c-3T3 cells for resistance to growth inhibition by IFN-beta and analyzed the phenotypes of resulting clonal lines (called IRB cells) with respect to PDGF signal transduction. Although selected only for IFN resistance, the IRB cells were found to be defective for induction of growth-related genes c-fos, c-myc and JE in response to PDGF. This block to signal transduction was not due to loss or inactivation of PDGF receptors, as immunoprecipitation of PDGF receptors with antiphosphotyrosine antibodies showed them to be present at equal levels in the BALB/c-3T3 and IRB cells and to be autophosphorylated normally in response to PDGF. Furthermore, treatment with other peptide growth factors (PDGF-AA, fibroblast growth factor, and epidermal growth factor) also failed to induce c-fos, c-myc, or JE expression in IRB cells. All of these growth factors, however, were able to induce another early growth-related gene, Egr-1. The block to signaling was not due to a defect in inositol phosphate metabolism, as PDGF treatment induced normal calcium mobilization and phosphotidylinositol-3-kinase activation in these cells. Activation of protein kinase C by phorbol esters did induce c-fos, c-myc, and JE in IRB cells, indicating that signalling pathways distal to this enzyme remained intact. We have previously shown that IFN-inducible enzyme activities, including double-stranded RNA-dependent eIF2 kinase and 2',5'-oligoadenylate synthetase, are normal in IRB cells. The finding that the induction of multiple growth-related genes by several independent growth factors is inhibited in these IFN-resistant cells suggests that there is a second messenger common to both growth factor and IFN signaling pathways and that this messenger is defective in these cells.

scholarly journals BALB/c-3T3 fibroblasts resistant to growth inhibition by beta interferon exhibit aberrant platelet-derived growth factor, epidermal growth factor, and fibroblast growth factor signal transduction

1991 ◽  
Vol 11 (6) ◽  
pp. 3148-3154
Author(s):  
L J Mundschau ◽  
D V Faller
Keyword(s):  
Signal Transduction ◽  
Growth Factors ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Signal Transduction Pathway ◽  
Platelet Derived Growth Factor ◽  
Fibroblast Growth ◽  
Transduction Pathway ◽  
Double Stranded Rna ◽  
Epidermal Growth

Several lines of evidence now exist to suggest an interaction between the platelet-derived growth factor (PDGF) growth-stimulatory signal transduction pathway and the beta interferon (IFN-beta) growth-inhibitory signal transduction pathway. The most direct examples are inhibition of PDGF-mediated gene induction and mitogenesis by IFN-beta and the effects of activators and inhibitors of the IFN-inducible double-stranded RNA-dependent eIF2 kinase on expression of PDGF-inducible genes. To further investigate the nature of this PDGF/IFN-beta interaction, we selected BALB/c-3T3 cells for resistance to growth inhibition by IFN-beta and analyzed the phenotypes of resulting clonal lines (called IRB cells) with respect to PDGF signal transduction. Although selected only for IFN resistance, the IRB cells were found to be defective for induction of growth-related genes c-fos, c-myc and JE in response to PDGF. This block to signal transduction was not due to loss or inactivation of PDGF receptors, as immunoprecipitation of PDGF receptors with antiphosphotyrosine antibodies showed them to be present at equal levels in the BALB/c-3T3 and IRB cells and to be autophosphorylated normally in response to PDGF. Furthermore, treatment with other peptide growth factors (PDGF-AA, fibroblast growth factor, and epidermal growth factor) also failed to induce c-fos, c-myc, or JE expression in IRB cells. All of these growth factors, however, were able to induce another early growth-related gene, Egr-1. The block to signaling was not due to a defect in inositol phosphate metabolism, as PDGF treatment induced normal calcium mobilization and phosphotidylinositol-3-kinase activation in these cells. Activation of protein kinase C by phorbol esters did induce c-fos, c-myc, and JE in IRB cells, indicating that signalling pathways distal to this enzyme remained intact. We have previously shown that IFN-inducible enzyme activities, including double-stranded RNA-dependent eIF2 kinase and 2',5'-oligoadenylate synthetase, are normal in IRB cells. The finding that the induction of multiple growth-related genes by several independent growth factors is inhibited in these IFN-resistant cells suggests that there is a second messenger common to both growth factor and IFN signaling pathways and that this messenger is defective in these cells.

Platelet-Derived Growth Factor-BB Stimulated Cell Migration Mediated Through p38 Signal Transduction Pathway in Periodontal Cells

2003 ◽  
Vol 74 (9) ◽  
pp. 1320-1328 ◽  
Author(s):  
Angel K. Ray ◽  
Anne C. Jones ◽  
David L. Carnes ◽  
David L. Cochran ◽  
James T. Mellonig ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Migration ◽  
Growth Factor ◽  
Signal Transduction Pathway ◽  
Platelet Derived Growth Factor ◽  
Transduction Pathway

Evidence for a novel signal transduction pathway activated by platelet-derived growth factor and by double-stranded RNA

1989 ◽  
Vol 9 (4) ◽  
pp. 1705-1713
Author(s):  
D J Hall ◽  
S D Jones ◽  
D R Kaplan ◽  
M Whitman ◽  
B J Rollins ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Growth Factor ◽  
Signal Transduction Pathway ◽  
Platelet Derived Growth Factor ◽  
Secretory Proteins ◽  
Transduction Pathway ◽  
Double Stranded Rna ◽  
3T3 Fibroblasts ◽  
Receptor Signal ◽  
Inducible Genes

Platelet-derived growth factor (PDGF) and the synthetic double-stranded RNA poly(I).poly(C) [poly(I.C)] stimulate transcription of the JE gene in BALB/c-3T3 fibroblasts. The response of JE to poly(I.C) does not appear to be channeled through any known component of the PDGF receptor signal transduction apparatus. In addition, JE sequences upstream of the transcription start site are devoid of previously identified poly(I.C)-responsive elements, such as those found in the beta-interferon gene. These data suggest that a novel signal transduction pathway regulates the JE response to PDGF and double-stranded RNA. The c-myc and c-fos proto-oncogenes also respond to this pathway but with poor efficiency. However, this pathway operates very efficiently on other PDGF-inducible genes that encode the secretory proteins KC and M-CSF.

scholarly journals Evidence for a novel signal transduction pathway activated by platelet-derived growth factor and by double-stranded RNA.

1989 ◽  
Vol 9 (4) ◽  
pp. 1705-1713 ◽  
Author(s):  
D J Hall ◽  
S D Jones ◽  
D R Kaplan ◽  
M Whitman ◽  
B J Rollins ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Growth Factor ◽  
Signal Transduction Pathway ◽  
Platelet Derived Growth Factor ◽  
Secretory Proteins ◽  
Transduction Pathway ◽  
Double Stranded Rna ◽  
3T3 Fibroblasts ◽  
Receptor Signal ◽  
Inducible Genes

Platelet-derived growth factor (PDGF) and the synthetic double-stranded RNA poly(I).poly(C) [poly(I.C)] stimulate transcription of the JE gene in BALB/c-3T3 fibroblasts. The response of JE to poly(I.C) does not appear to be channeled through any known component of the PDGF receptor signal transduction apparatus. In addition, JE sequences upstream of the transcription start site are devoid of previously identified poly(I.C)-responsive elements, such as those found in the beta-interferon gene. These data suggest that a novel signal transduction pathway regulates the JE response to PDGF and double-stranded RNA. The c-myc and c-fos proto-oncogenes also respond to this pathway but with poor efficiency. However, this pathway operates very efficiently on other PDGF-inducible genes that encode the secretory proteins KC and M-CSF.

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