scholarly journals Stat6 and Jak1 Are Common Elements in Platelet-derived Growth Factor and Interleukin-4 Signal Transduction Pathways in NIH 3T3 Fibroblasts

1996 ◽  
Vol 271 (36) ◽  
pp. 22175-22182 ◽  
Author(s):  
Bharvin K. R. Patel ◽  
Ling-Mei Wang ◽  
Chong-Chou Lee ◽  
William G. Taylor ◽  
Jacalyn H. Pierce ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Interleukin 4 ◽  
Signal Transduction Pathways ◽  
Common Elements ◽  
3T3 Fibroblasts ◽  
Nih 3T3

The erbB-2 mitogenic signaling pathway: tyrosine phosphorylation of phospholipase C-gamma and GTPase-activating protein does not correlate with erbB-2 mitogenic potency

1991 ◽  
Vol 11 (4) ◽  
pp. 2040-2048
Author(s):  
F Fazioli ◽  
U H Kim ◽  
S G Rhee ◽  
C J Molloy ◽  
O Segatto ◽  
...  
Keyword(s):  
Growth Factor ◽  
Dna Synthesis ◽  
Phospholipase C ◽  
Signaling Pathway ◽  
Tyrosine Phosphorylation ◽  
Platelet Derived Growth Factor ◽  
Mitogenic Signaling ◽  
Gtpase Activating Protein ◽  
3T3 Fibroblasts ◽  
Nih 3T3

The erbB-2 gene product, gp185erbB-2, unlike the structurally related epidermal growth factor (EGF) receptor (EGFR), exhibits constitutive kinase and transforming activity. We used a chimeric EGFR/erbB-2 expression vector to compare the mitogenic signaling pathway of the erbB-2 kinase with that of the EGFR, at similar levels of expression, in response to EGF stimulation. The EGFR/erbB-2 chimera was significantly more active in inducing DNA synthesis than the EGFR when either was expressed in NIH 3T3 cells. Analysis of biochemical pathways implicated in signal transduction by growth factor receptors indicated that both phospholipase C type gamma (PLC-gamma) and the p21ras GTPase-activating protein (GAP) are substrates for the erbB-2 kinase in NIH 3T3 fibroblasts. However, under conditions in which activation of the erbB-2 kinase induced DNA synthesis at least fivefold more efficiently than the EGFR, the levels of erbB-2- or EGFR-induced tyrosine phosphorylation of PLC-gamma and GAP were comparable. In addition, the stoichiometry of tyrosine phosphorylation of these putative substrates by erbB-2 appeared to be at least an order of magnitude lower than that induced by platelet-derived growth factor receptors at comparable levels of mitogenic potency. Thus, our results indicate that differences in tyrosine phosphorylation of PLC-gamma and GAP do not account for the differences in mitogenic activity of the erbB-2 kinase compared with either the EGFR or platelet-derived growth factor receptor in NIH 3T3 fibroblasts.

scholarly journals The erbB-2 mitogenic signaling pathway: tyrosine phosphorylation of phospholipase C-gamma and GTPase-activating protein does not correlate with erbB-2 mitogenic potency.

1991 ◽  
Vol 11 (4) ◽  
pp. 2040-2048 ◽  
Author(s):  
F Fazioli ◽  
U H Kim ◽  
S G Rhee ◽  
C J Molloy ◽  
O Segatto ◽  
...  
Keyword(s):  
Growth Factor ◽  
Dna Synthesis ◽  
Phospholipase C ◽  
Signaling Pathway ◽  
Tyrosine Phosphorylation ◽  
Platelet Derived Growth Factor ◽  
Mitogenic Signaling ◽  
Gtpase Activating Protein ◽  
3T3 Fibroblasts ◽  
Nih 3T3

The erbB-2 gene product, gp185erbB-2, unlike the structurally related epidermal growth factor (EGF) receptor (EGFR), exhibits constitutive kinase and transforming activity. We used a chimeric EGFR/erbB-2 expression vector to compare the mitogenic signaling pathway of the erbB-2 kinase with that of the EGFR, at similar levels of expression, in response to EGF stimulation. The EGFR/erbB-2 chimera was significantly more active in inducing DNA synthesis than the EGFR when either was expressed in NIH 3T3 cells. Analysis of biochemical pathways implicated in signal transduction by growth factor receptors indicated that both phospholipase C type gamma (PLC-gamma) and the p21ras GTPase-activating protein (GAP) are substrates for the erbB-2 kinase in NIH 3T3 fibroblasts. However, under conditions in which activation of the erbB-2 kinase induced DNA synthesis at least fivefold more efficiently than the EGFR, the levels of erbB-2- or EGFR-induced tyrosine phosphorylation of PLC-gamma and GAP were comparable. In addition, the stoichiometry of tyrosine phosphorylation of these putative substrates by erbB-2 appeared to be at least an order of magnitude lower than that induced by platelet-derived growth factor receptors at comparable levels of mitogenic potency. Thus, our results indicate that differences in tyrosine phosphorylation of PLC-gamma and GAP do not account for the differences in mitogenic activity of the erbB-2 kinase compared with either the EGFR or platelet-derived growth factor receptor in NIH 3T3 fibroblasts.

Functional Proteomics Analysis of Signal Transduction Pathways of the Platelet-Derived Growth Factor β Receptor†

Biochemistry ◽  
1999 ◽  
Vol 38 (6) ◽  
pp. 1757-1764 ◽  
Author(s):  
Vukic Soskic ◽  
Matthias Görlach ◽  
Slobodan Poznanovic ◽  
Frank D. Boehmer ◽  
Jasminka Godovac-Zimmermann
Keyword(s):  
Signal Transduction ◽  
Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Signal Transduction Pathways ◽  
Functional Proteomics ◽  
Proteomics Analysis ◽  
Β Receptor

scholarly journals Overexpression of phospholipase C-gamma in NIH 3T3 fibroblasts results in increased phosphatidylinositol hydrolysis in response to platelet-derived growth factor and basic fibroblast growth factor.

1990 ◽  
Vol 10 (11) ◽  
pp. 6069-6072 ◽  
Author(s):  
A Cuadrado ◽  
C J Molloy
Keyword(s):  
Growth Factor ◽  
Phospholipase C ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Phosphoinositide Metabolism ◽  
Fibroblast Growth ◽  
3T3 Fibroblasts ◽  
Phospholipase C Gamma ◽  
Nih 3T3

Overexpression of phospholipase C-gamma in fibroblasts led to increased tyrosine phosphorylation of this enzyme in response to platelet-derived growth factor and basic fibroblast growth factor. This correlated with increased phosphoinositide release but not with enhanced mitogenicity. Thus, phospholipase C-gamma-mediated phosphoinositide metabolism may not be limiting in the signaling pathways initiated by these growth factors.

scholarly journals Nckβ Adapter Regulates Actin Polymerization in NIH 3T3 Fibroblasts in Response to Platelet-Derived Growth Factor bb

2000 ◽  
Vol 20 (21) ◽  
pp. 7867-7880 ◽  
Author(s):  
Min Chen ◽  
Hongyun She ◽  
Airie Kim ◽  
David T. Woodley ◽  
Wei Li
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinases ◽  
Intracellular Signaling ◽  
Actin Polymerization ◽  
Platelet Derived Growth Factor ◽  
Tyrosine Kinase Signaling ◽  
Membrane Ruffling ◽  
3T3 Fibroblasts ◽  
Membrane Bound ◽  
Nih 3T3

ABSTRACT The SH3-SH3-SH3-SH2 adapter Nck represents a two-gene family that includes Nckα (Nck) and Nckβ (Grb4/Nck2), and it links receptor tyrosine kinases to intracellular signaling networks. The function of these mammalian Nck genes has not been established. We report here a specific role for Nckβ in platelet-derived growth factor (PDGF)-induced actin polymerization in NIH 3T3 cells. Overexpression of Nckβ but not Nckα blocks PDGF-stimulated membrane ruffling and formation of lamellipoda. Mutation in either the SH2 or the middle SH3 domain of Nckβ abolishes its interfering effect. Nckβ binds at Tyr-1009 in human PDGF receptor β (PDGFR-β) which is different from Nckα's binding site, Tyr-751, and does not compete with phosphatidylinositol-3 kinase for binding to PDGFR. Microinjection of an anti-Nckβ but not an anti-Nckα antibody inhibits PDGF-stimulated actin polymerization. Constitutively membrane-bound Nckβ but not Nckα blocks Rac1-L62-induced membrane ruffling and formation of lamellipodia, suggesting that Nckβ acts in parallel to or downstream of Rac1. This is the first report of Nckβ's role in receptor tyrosine kinase signaling to the actin cytoskeleton.

scholarly journals Differential effects of platelet-derived growth factor, serum and bombesin on phospholipase D-mediated hydrolysis of phosphatidylethanolamine in NIH 3T3 fibroblasts

1992 ◽  
Vol 285 (1) ◽  
pp. 229-233 ◽  
Author(s):  
Z Kiss
Keyword(s):  
Growth Factor ◽  
Phospholipase D ◽  
Calf Serum ◽  
Platelet Derived Growth Factor ◽  
Maximal Effect ◽  
3T3 Fibroblasts ◽  
Kinase C ◽  
Nih 3T3 ◽  
Hydrolysis Of ◽  
Fold Stimulation

In previous studies, activators of protein kinase C, sphingosine, ATP and various oncogenes were each found to enhance phospholipase D-mediated hydrolysis of phosphatidylethanolamine (PtdEtn) in NIH 3T3 fibroblasts. Here I examined possible stimulation of PtdEtn hydrolysis by various growth-stimulatory agents, including serum, bombesin, platelet-derived growth factor (PDGF), fibroblast growth factor (FGF) and insulin. Treatment of NIH 3T3 fibroblasts, prelabelled with [14C]Etn or [32P]PtdEtn, with PDGF-BB resulted in enhanced formation of [14C]Etn or [32P]phosphatidic acid from the respective labelled cellular pools of PtdEtn. A maximal effect (approximately 3-fold stimulation) on PtdEtn hydrolysis was obtained with 50 ng of PDGF/ml after 5 min of treatment. Phosphatidylcholine (PtdCho) was also hydrolysed, although less extensively than PtdEtn, in PDGF-stimulated cells. PDGF-stimulate hydrolysis of both PtdEtn and PtdCho was prevented by prolonged (30 h) treatment of cells with 400 nM-phorbol 12-myristate 13-acetate (PMA). Similar to PDGF, fetal calf serum (1-10%) also stimulated PtdEtn hydrolysis. However, in contrast to PDGF, the effect of serum on PtdEtn hydrolysis (i) was not diminished by pretreatment with PMA, and (ii) was synergistic with that of PMA after a 1 h incubation. Compared with PDGF and serum, bombesin had less effect on PtdEtn hydrolysis, while FGF and insulin had no effects at all. In contrast to PDGF or serum, bombesin inhibited the effect of PMA on PtdEtn hydrolysis.

Overexpression of phospholipase C-gamma in NIH 3T3 fibroblasts results in increased phosphatidylinositol hydrolysis in response to platelet-derived growth factor and basic fibroblast growth factor

1990 ◽  
Vol 10 (11) ◽  
pp. 6069-6072
Author(s):  
A Cuadrado ◽  
C J Molloy
Keyword(s):  
Growth Factor ◽  
Phospholipase C ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Phosphoinositide Metabolism ◽  
Fibroblast Growth ◽  
3T3 Fibroblasts ◽  
Phospholipase C Gamma ◽  
Nih 3T3

Overexpression of phospholipase C-gamma in fibroblasts led to increased tyrosine phosphorylation of this enzyme in response to platelet-derived growth factor and basic fibroblast growth factor. This correlated with increased phosphoinositide release but not with enhanced mitogenicity. Thus, phospholipase C-gamma-mediated phosphoinositide metabolism may not be limiting in the signaling pathways initiated by these growth factors.

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