Cross-talk between receptors with intrinsic tyrosine kinase activity and α1b-adrenoceptors

2000 ◽  
Vol 350 (2) ◽  
pp. 413-419 ◽  
Author(s):  
Luz DEL CARMEN MEDINA ◽  
José VÁZQUEZ-PRADO ◽  
J. Adolfo GARCÍA-SÁINZ
Keyword(s):  
Protein Kinase C ◽  
Growth Factors ◽  
Growth Factor ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Functional Coupling ◽  
Kinase C ◽  
Epidermal Growth ◽  
Phosphoinositide 3 Kinase ◽  
And Function

The effect of epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) on the phosphorylation and function of α1b-adrenoceptors transfected into Rat-1 fibroblasts was studied. EGF and PDGF increased the phosphorylation of these adrenoceptors. The effect of EGF was blocked by tyrphostin AG1478 and that of PDGF was blocked by tyrphostin AG1296, inhibitors of the intrinsic tyrosine kinase activities of the receptors for these growth factors. Wortmannin, an inhibitor of phosphoinositide 3-kinase, blocked the α1b-adrenoceptor phosphorylation induced by EGF but not that induced by PDGF. Inhibition of protein kinase C blocked the adrenoceptor phosphorylation induced by EGF and PDGF. The ability of noradrenaline to increase [35S]guanosine 5´-[γ-thio]triphosphate ([35S]GTP[S]) binding in membrane preparations was used as an index of the functional coupling of the α1b-adrenoceptors and G-proteins. Noradrenaline-stimulated [35S]GTP[S] binding was markedly decreased in membranes from cells pretreated with EGF or PDGF. Our data indicate that: (i) activation of EGF and PDGF receptors induces phosphorylation of α1b-adrenoceptors, (ii) phosphatidylinositol 3-kinase is involved in the EGF response, but does not seem to play a major role in the action of PDGF, (iii) protein kinase C mediates this action of both growth factors and (iv) the phosphorylation of α1b-adrenoceptors induced by EGF and PDGF is associated with adrenoceptor desensitization.

Mechanism of sodium transport inhibition by epidermal growth factor in cortical collecting ducts

1991 ◽  
Vol 261 (5) ◽  
pp. F896-F903 ◽  
Author(s):  
V. M. Vehaskari ◽  
J. Herndon ◽  
L. L. Hamm
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Epidermal Growth Factor ◽  
Na Transport ◽  
Kinase C ◽  
Transport Inhibition ◽  
Collecting Ducts ◽  
Epidermal Growth

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.

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

1991 ◽  
Vol 278 (3) ◽  
pp. 679-687 ◽  
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.

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

1994 ◽  
Vol 46 (3) ◽  
pp. 690-695 ◽  
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

scholarly journals Neuroprotection by Peptide Growth Factors against Anoxia and Nitric Oxide Toxicity Requires Modulation of Protein Kinase C

1995 ◽  
Vol 15 (3) ◽  
pp. 440-449 ◽  
Author(s):  
Kenneth Maiese ◽  
Lauraine Boccone
Keyword(s):  
Nitric Oxide ◽  
Signal Transduction ◽  
Protein Kinase C ◽  
Growth Factors ◽  
Growth Factor ◽  
Protein Kinase ◽  
Neuronal Degeneration ◽  
Kinase C ◽  
Peptide Growth Factors ◽  
Pkc Activation

Basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) are neuroprotective during anoxia and nitric oxide (NO) toxicity. Signal transduction systems that modulate protein kinase C (PKC) also can modulate the toxic effects of anoxia and NO. We therefore examined whether PKC was involved in the protective effects of bFGF and EGF during anoxia and NO toxicity. Down-regulation or inhibition of PKC activity before anoxia or NO exposure prevented hippocampal neuronal degeneration. Yet, this protective effect of inhibition of PKC activity was not present with the coadministration of growth factors. Combined inhibition of PKC activity and application of bFGF or EGF lessened the protective mechanisms of the growth factors. In addition, the protective ability of the growth factors was lost during anoxia and NO exposure with the activation of PKC, suggesting that at least a minimal degree of PKC activation is necessary for growth factor protection. Although modulation of PKC activity may be a necessary prerequisite for protection against anoxia and NO toxicity by bFGF and EGF, only inhibition of PKC activity, rather than application of the growth factors, was protective following exposure to NO. These results suggest that the mechanism of protection by bFGF and EGF during anoxia and NO toxicity appears initially to be dependent on a minimum degree of PKC activation, but that other signal transduction pathways independent of PKC also may mediate protection by peptide growth factors.

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