scholarly journals Protein Kinase C α-mediated Negative Feedback Regulation Is Responsible for the Termination of Insulin-like Growth Factor I-induced Activation of Nuclear Phospholipase C β1 in Swiss 3T3 Cells

2001 ◽  
Vol 276 (18) ◽  
pp. 14980-14986 ◽  
Author(s):  
Aimin Xu ◽  
Yu Wang ◽  
Lance Yi Xu ◽  
R. Stewart Gilmour
Keyword(s):  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Phospholipase C ◽  
Negative Feedback ◽  
Feedback Regulation ◽  
3T3 Cells ◽  
Negative Feedback Regulation ◽  
Factor I ◽  
Kinase C

scholarly journals Bombesin and platelet-derived growth factor stimulate formation of inositol phosphates and Ca2+ mobilization in Swiss 3T3 cells by different mechanisms

1989 ◽  
Vol 258 (1) ◽  
pp. 177-185 ◽  
Author(s):  
D M Blakeley ◽  
A N Corps ◽  
K D Brown
Keyword(s):  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Phorbol Esters ◽  
Inositol Phosphates ◽  
Platelet Derived Growth Factor ◽  
3T3 Cells ◽  
Kinase C ◽  
Swiss 3T3 ◽  
Stimulation Of

Highly purified platelet-derived growth factor (PDGF) or recombinant PDGF stimulate DNA synthesis in quiescent Swiss 3T3 cells. The dose-response curves for the natural and recombinant factors were similar, with half-maximal responses at 2-3 ng/ml and maximal responses at approx. 10 ng/ml. Over this dose range, both natural and recombinant PDGF stimulated a pronounced accumulation of [3H]inositol phosphates in cells labelled for 72 h with [3H]inositol. In addition, mitogenic concentrations of PDGF stimulated the release of 45Ca2+ from cells prelabelled with the radioisotope. However, in comparison with the response to the peptide mitogens bombesin and vasopressin, a pronounced lag was evident in both the generation of inositol phosphates and the stimulation of 45Ca2+ efflux in response to PDGF. Furthermore, although the bombesin-stimulated efflux of 45Ca2+ was independent of extracellular Ca2+, the PDGF-stimulated efflux was markedly inhibited by chelation of external Ca2+ by using EGTA. Neither the stimulation of formation of inositol phosphates nor the stimulation of 45Ca2+ efflux in response to PDGF were affected by tumour-promoting phorbol esters such as 12-O-tetradecanoylphorbol 13-acetate (TPA). In contrast, TPA inhibited phosphoinositide hydrolysis and 45Ca2+ efflux stimulated by either bombesin or vasopressin. Furthermore, whereas formation of inositol phosphates in response to both vasopressin and bombesin was increased in cells in which protein kinase C had been down-modulated by prolonged exposure to phorbol esters, the response to PDGF was decreased in these cells. These results suggest that, in Swiss 3T3 cells, PDGF receptors are coupled to phosphoinositidase activation by a mechanism that does not exhibit protein kinase C-mediated negative-feedback control and which appears to be fundamentally different from the coupling mechanism utilized by the receptors for bombesin and vasopressin.

scholarly journals Protein Kinase C-δ Is an Important Signaling Molecule in Insulin-Like Growth Factor I Receptor-Mediated Cell Transformation

1998 ◽  
Vol 18 (10) ◽  
pp. 5888-5898 ◽  
Author(s):  
Weiqun Li ◽  
Yi-Xing Jiang ◽  
Jiachang Zhang ◽  
Lilian Soon ◽  
Lawrence Flechner ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Transcriptional Activation ◽  
Cell Transformation ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Kinase C ◽  
Growth Factor I ◽  
Nih 3T3

ABSTRACT To investigate the potential role of protein kinase C-δ (PKC-δ) in insulin-like growth factor I receptor (IGF-IR)-mediated cell transformation, an oncogenic gag-IGF-IR β-fusion receptor lacking the entire extracellular domain, which was designated NM1, and a full-length IGF-IR were coexpressed with either wild-type PKC-δ (PKC-δWT) or an ATP-binding mutant of PKC-δ (PKC-δK376R) in NIH 3T3 fibroblasts. While overexpression of PKC-δWT did not affect NM1- and IGF-IR-induced focus and colony formation of NIH 3T3 cells, expression of PKC-δK376R severely impaired these events. In contrast, NM1-mediated cell growth in monolayer was not affected by coexpressing PKC-δK376R. PKC-δWT and PKC-δK376R were constitutively phosphorylated on a tyrosine residue(s) in the NM1- and IGF-IR-expressing cells and were associated with them in an IGF-I-independent manner. Activated IGF-IR was able to phosphorylate purified PKC-δ in vitro and stimulated its kinase activity. Furthermore, the level of endogenous PKC-δ protein was up-regulated through transcriptional activation in response to long-term IGF-IR activation. Taken together, our results demonstrate that PKC-δ plays an important role in IGF-IR-mediated cell transformation, probably via association of the receptor with PKC-δ and its activation through protein up-regulation and tyrosine phosphorylation. Competition with endogenous PKC-δ for NM1 and IGF-IR association by PKC-δK376R is probably an important mechanism underlying the PKC-δK376R-mediated inhibition of cell transformation by NM1 and IGF-IR.

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