EGF receptor affinity is regulated by intracellular calcium and protein kinase C

Fearn, Jeffrey C.; King, A C

doi:10.1016/0092-8674(85)90359-9

Cited by 113 publications

(48 citation statements)

References 35 publications

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“…A similar effect of internalisation catalysed by phorbol esters has been noted for the EGF receptor [194,1951. lnterestingly, mutation of the major protein kinase C phosphorylation site, Thr654-Ala654, whilst not affecting the ability of EGF itself to stimulate receptor internalization, did block the ability of phorbol esters to achieve this.…”

Section: Protein Kinase C Activation and Receptor Down-regulationmentioning

confidence: 55%

‘Crosstalk’: a pivotal role for protein kinase C in modulating relationships between signal transduction pathways

Houslay

1991

European Journal of Biochemistry

328

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Over the past 20 years we have seen a phenomenal increase in our understanding ofthe diversity and the molecular mechanism of action of signal transduction systems. Now we are faced with a cell being provided with a myriad of cell surface receptors, each connected to particular signal transduction systems. The very complexity of such systems, together with the need of the cell to monitor and respond to a variety of external stimuli, poses the question as to what overall controls are placed upon these various transduction mechanisms and how they might relate to each other. At one extreme, we can envisage that pathways might be isolated completely from each other and thus function in an an apparent 'vacuum'. On the other hand, we can envisage 'cross-talk' between the various pathways linking each into an adaptable network array. Such a network, linking distinct signalling systems, would offer the cell a sophisticated ability to sense multiple environmental signals impinging upon it, thus providing a means of adapting or regulating its response to a particular range of effectors. In this way the cell might respond to the relative concentrations of various signals, taking into account the particular point in time when it first experienced a specific signal, together with the absolute length of time it was exposed to it. Such parameters having markedly different effects on cellular behaviour. Thus one might envisage that both the 'quantity' and the 'quality' of information flowing through any particular signal transduction system might be altered by the functioning of other transduction systems which were linked to form such an interactive network. A cell controlled in such a fashion could be regarded as being capable of 'learning', Correspondence to

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Section: Protein Kinase C Activation and Receptor Down-regulationmentioning

confidence: 55%

‘Crosstalk’: a pivotal role for protein kinase C in modulating relationships between signal transduction pathways

Houslay

1991

European Journal of Biochemistry

328

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“…In certain cell types, optimal proliferation appears to be incompatible with the fully differentiated phenotype (3,18,19,21,46,47 (15), probably through phosphorylation of the receptor (15,17,23 (13,32) and activation of the phosphatidylinositol pathway (2,30) have also been reported. The striking increase in c-fos RNA observed rapidly as well is the earliest reported alteration at the level of gene expression.…”

Section: Discussionmentioning

confidence: 99%

The calcium signal for BALB/MK keratinocyte terminal differentiation counteracts epidermal growth factor (EGF) very early in the EGF-induced proliferative pathway.

et al. 1988

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BALB/MK mouse epidermal keratinocytes require epidermal growth factor (EGF) for proliferation and terminally differentiate in response to high calcium concentrations. We show that EGF is an extremely potent mitogen, causing BALB/MK cultures to enter the cell cycle in a synchronous manner associated with a greater than 100-fold increase in DNA synthesis. Analysis of the expression of proto-oncogenes which have been reported to be activated during the cascade of events following growth factor stimulation of fibroblasts or lymphoid cells revealed a very rapid but transient 100-fold increase in c-fos RNA but little or no effect on the other proto-oncogenes analyzed. Exposure of EGF-synchronized BALB/MK cells to high levels of calcium was associated with a striking decrease in the early burst of c-fos RNA as well as the subsequent peak of cell DNA synthesis. Since the inhibitory effect of high calcium on c-fos RNA expression was measurable within 30 mi, our studies imply that the EGF proliferative and calcium differentiation signals must interact very early in the pathway of EGF-induced proliferation. Our results also establish that c-fos RNA modulation is an importent early marker of cell proliferation in epithelial as well as mesenchymal cells.

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“…This suggestion is further supported by the observation that phorbol esters and EGF can inhibit oestrogen production in granulosa cells [8,161. Due to the limited number of experiments carried out with gonadal cells, it is unknown which mechanisms may play a role in protein kinase Cmediated regulation of oestradiol production in gonadal cells. However, in KB cells calcium and protein kinase C can reduce the affinity of the EGF receptor for EGF, probably via receptor phosphorylation [20,21]. It has been reported that Sertoli cells can secrete a growth factor that can block binding of EGF to EGF receptors [22].…”

Section: Discussionmentioning

confidence: 99%

Modulation of stimulatory action of follicle stimulating hormone (FSH) and inhibitory action of epidermal growth factor (EGF) on aromatase activity in Sertoli cells by calcium

Mallea¹,

Machado²,

Navaroli³

et al. 1987

FEBS Letters

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Aromatization of testosterone by cultured Sertoli cells isolated from immature rats was stimulated more than 7-fold by follicle stimulating hormone (FSH) or dcAMP. The effects of FSH and dcAMP could be partly inhibited by epidermal growth factor (EGF) in a dose-dependent manner (IDs0 0.5 nM). The phorbol ester 4fl-phorbol-12-myristate-13-acetate (PMA) could also inhibit aromatase activity in a fashion similar to EGF. When 3 mM EGTA was present in the culture medium, the inhibitory effect of EGF was abolished but the stimulatory effect of FSH or dcAMP was magnified. These results suggest that EGF exerts a negative control on aromatase via calcium and protein kinase C. The abolishment of the inhibitory effect of EGF and the enhancement of the stimulatory effect of FSH or dcAMP by a calcium deficiency may be an indication that growth factors produced by Sertoli cells negatively control FSH-induced responses in an autocrine fashion.

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EGF receptor affinity is regulated by intracellular calcium and protein kinase C

Cited by 113 publications

References 35 publications

‘Crosstalk’: a pivotal role for protein kinase C in modulating relationships between signal transduction pathways

‘Crosstalk’: a pivotal role for protein kinase C in modulating relationships between signal transduction pathways

The calcium signal for BALB/MK keratinocyte terminal differentiation counteracts epidermal growth factor (EGF) very early in the EGF-induced proliferative pathway.

Modulation of stimulatory action of follicle stimulating hormone (FSH) and inhibitory action of epidermal growth factor (EGF) on aromatase activity in Sertoli cells by calcium

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