Epidermal Growth Factor Induces Fibronectin Expression in Human Dermal Fibroblasts via Protein Kinase C δ Signaling Pathway

Epidermal growth factor (EGF) inhibits Na transport in the cortical collecting ducts (CCD). To gain insight into the signal transduction of this effect, several potential mechanisms were examined in rabbit CCD perfused in vitro. Pretreatment with pertussis toxin, indomethacin, or the protein kinase C inhibitor H7 did not prevent the acute 34-50% decrease in lumen-to-bath 22Na flux (JNa) on exposure to peritubular EGF, indicating that the inhibition is not mediated by a Gi protein, prostaglandin E2 (PGE2), or protein kinase C. Inhibition of the basolateral Na-H exchanger was also without an effect. Lowering the bath Ca concentration from 1.2 to 0.11 mM did not prevent the inhibition of JNa by EGF (JNa decreased significantly by 38.7 +/- 6.9% and 29.1 +/- 5.3%, respectively); in contrast, reduction of the bath free Ca to 0.005 mM totally abolished the effect of EGF. The response to EGF was also assessed in the setting of chronic stimulation of Na transport; inhibition of JNa by EGF was still observed in CCD from remnant kidneys and in CCD from mineralocorticoid-treated rabbits. The results demonstrate that the inhibition of CCD Na transport by EGF is dependent on peritubular Ca. This suggests that the signal transduction involves Ca influx across the basolateral membrane and that increased cytosolic free Ca may be a common pathway for the counterregulatory control of Na reabsorption by several agonists.

Download Full-text

Regulation of epidermal-growth-factor-receptor signal transduction by cis-unsaturated fatty acids. Evidence for a protein kinase C-independent mechanism

Biochemical Journal ◽

10.1042/bj2780679 ◽

1991 ◽

Vol 278 (3) ◽

pp. 679-687 ◽

Cited By ~ 26

Author(s):

X Casabiell ◽

A Pandiella ◽

F F Casanueva

Keyword(s):

Signal Transduction ◽

Fatty Acids ◽

Protein Kinase C ◽

Oleic Acid ◽

Growth Factor ◽

Protein Kinase ◽

Epidermal Growth Factor ◽

Cell Lines ◽

Kinase C ◽

Epidermal Growth

The effect of acute treatment with non-esterified fatty acids (NEFA) on transmembrane signalling has been investigated in three different cell lines. In EGFR T17 cells, pretreatment with cis-unsaturated (oleic and palmitoleic acids) NEFA, but not with saturated or trans-unsaturated NEFA, inhibited the epidermal-growth-factor (EGF)-induced increases in cytosolic [Ca2+], membrane potential and Ins(1,4,5)P3 generation. The blocking effect was found to be time- and dose-dependent and rapidly reversible after washout. However, oleic acid treatment did not block either binding of 125I-EGF to its receptor or EGF-induced autophosphorylation of the EGF receptor. The mechanism of action of NEFA could not be attributed to protein kinase C activation, since (i) down-regulation of the enzyme by long-term treatment with phorbol esters did not prevent blockade by oleic acid, and (ii) the effects of acutely administered phorbol ester and oleic acid were additive. In this cell line, signalling at bradykinin and bombesin receptors was also impaired by oleic acid. In A431 cells, oleic acid also blocked signal transduction at the EGF and B2 bradykinin receptors. Finally, in PC12 cells, oleic acid blocked the Ca2+ influx mediated by the activation of B2 bradykinin receptors. In conclusion: (1) NEFA block signal transduction by interfering with receptor-phospholipase C or phospholipase C-substrate interaction without preventing ligand binding; (2) NEFA do not act by a protein kinase C-mediated mechanism; (3) the effect of NEFA is dependent on their configuration rather than hydrophobicity or chain length; (4) this effect is evident in several different cell lines and receptor systems.

Download Full-text

Induction of heparin-binding epidermal growth factor-like growth factor mRNA by protein kinase C activators

Kidney International ◽

10.1038/ki.1994.322 ◽

1994 ◽

Vol 46 (3) ◽

pp. 690-695 ◽

Cited By ~ 17

Author(s):

Mian-Shin Tan ◽

Jer-Chia Tsai ◽

Yau-Jiunn Lee ◽

Hung-Chun Chen ◽

Shyi-Jang Shin ◽

...

Keyword(s):

Protein Kinase C ◽

Growth Factor ◽

Protein Kinase ◽

Epidermal Growth Factor ◽

Heparin Binding ◽

Kinase C ◽

Protein Kinase C Activators ◽

Epidermal Growth

Download Full-text

Epidermal Growth Factor Activates Phosphoinositide Turnover and Protein Kinase C in BALB/MK Keratinocytes

Molecular Endocrinology ◽

10.1210/mend-2-9-799 ◽

1988 ◽

Vol 2 (9) ◽

pp. 799-805 ◽

Cited By ~ 26

Author(s):

Jorge Moscat ◽

Christopher J. Molloy ◽

Timothy P. Fleming ◽

Stuart A. Aaronson

Keyword(s):

Protein Kinase C ◽

Growth Factor ◽

Protein Kinase ◽

Epidermal Growth Factor ◽

Phosphoinositide Turnover ◽

Kinase C ◽

Epidermal Growth

Download Full-text

Regulation of Proliferation and Apoptosis by Epidermal Growth Factor and Protein Kinase C in Human Ovarian Surface Epithelial Cells

Experimental Cell Research ◽

10.1006/excr.1998.4328 ◽

1999 ◽

Vol 246 (2) ◽

pp. 471-479 ◽

Cited By ~ 33

Author(s):

Maryanne McClellan ◽

Paul Kievit ◽

Nelly Auersperg ◽

Karin Rodland

Keyword(s):

Protein Kinase C ◽

Growth Factor ◽

Protein Kinase ◽

Epidermal Growth Factor ◽

Epithelial Cells ◽

Kinase C ◽

Proliferation And Apoptosis ◽

Regulation Of Proliferation ◽

Ovarian Surface Epithelial ◽

Epidermal Growth

Download Full-text

Epidermal Growth Factor Receptor and Protein Kinase C Signaling to ERK2

Journal of Biological Chemistry ◽

10.1074/jbc.m706624200 ◽

2008 ◽

Vol 283 (10) ◽

pp. 6241-6252 ◽

Cited By ~ 55

Author(s):

Christopher J. Caunt ◽

Caroline A. Rivers ◽

Becky L. Conway-Campbell ◽

Michael R. Norman ◽

Craig A. McArdle

Keyword(s):

Epidermal Growth Factor Receptor ◽

Protein Kinase C ◽

Growth Factor ◽

Protein Kinase ◽

Epidermal Growth Factor ◽

Growth Factor Receptor ◽

Kinase C ◽

Epidermal Growth

Download Full-text

Epidermal growth factor stimulation of stromelysin mRNA in rat fibroblasts requires induction of proto-oncogenes c-fos and c-jun and activation of protein kinase C.

Molecular and Cellular Biology ◽

10.1128/mcb.10.8.4284 ◽

1990 ◽

Vol 10 (8) ◽

pp. 4284-4293 ◽

Cited By ~ 121

Author(s):

S E McDonnell ◽

L D Kerr ◽

L M Matrisian

Keyword(s):

Protein Kinase C ◽

Growth Factor ◽

Protein Kinase ◽

Epidermal Growth Factor ◽

Kinase Activation ◽

Kinase C ◽

Protein Kinase C Activity ◽

Epidermal Growth ◽

Rat Fibroblasts ◽

Stimulation Of

Stromelysin (transin) is a secreted metalloprotease that is transcriptionally induced by a variety of growth factors and oncogenes. We examined the necessity of specific secondary (protein kinase C) and tertiary (c-fos and c-jun protein products) messengers in the transactivation of stromelysin gene expression by epidermal growth factor (EGF). Rat-1 fibroblasts exposed to antisense c-fos DNA or RNA demonstrated that c-fos expression was necessary for complete EGF induction of stromelysin expression. Similar results demonstrating the necessity of c-jun protein in the EGF induction of stromelysin were obtained. We also demonstrated that protein kinase C activation is required for the EGF induction of stromelysin, since phorbol ester desensitization of C kinase proteins abolished the ability of EGF to induce stromelysin mRNA, protein, and promoter activity. In reconstitution experiments, neither c-fos, c-jun, nor C kinase activation alone induced significant stromelysin expression. Overexpression of c-fos and c-jun was able to induce stromelysin to a level similar to that of the growth factor, and stimulation of protein kinase C activity augmented this induction. The data suggest that the EGF induction of stromelysin in rat fibroblasts procedes through a pathway involving c-fos, c-jun, and protein kinase C.

Download Full-text