Modulation of Epidermal Growth Factor Receptors on 3T3 Cells by Platelet-Derived Growth Factor

Wrann, Michael; Fox, C. Fred; Ross, Russell

doi:10.1126/science.6254158

Cited by 180 publications

(72 citation statements)

References 20 publications

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“…PDGF also was found to inhibit the binding of 125I-EGF to monolayers of these cells (Fig. 1) in a manner similar to that reported for other fibroblasts (4)(5)(6)(7)(8)(9). Addition of the tumor promoter PMA to the fibroblasts similarly caused a decrease in the binding of 125I-EGF (Fig.…”

supporting

confidence: 78%

“…Interestingly, this effect is also characteristic of tumor-promoting phorbol diesters such as 4p-phorbol 12/3-myristate 13a-acetate (PMA), which stimulate the growth of quiescent fibroblasts synergistically with EGF and insulin (2,3). An-other striking similarity between the actions of PDGF and phorbol diesters is a rapid inhibition of 125I-labeled EGF (125I-EGF) binding to the receptors ofcultured cells (4)(5)(6)(7)(8)(9)(10)(11)(12). In view of the similarity of these actions of PDGF and PMA on the EGF receptor, we considered the possibility that these two agents may have a similar mechanism of action.…”

mentioning

confidence: 99%

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Platelet-derived growth factor mimics phorbol diester action on epidermal growth factor receptor phosphorylation at threonine-654.

Davis¹,

Czech²

1985

Proc. Natl. Acad. Sci. U.S.A.

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Addition of platelet-derived growth factor (PDGF) to quiescent WI-38 human fetal lung fibroblasts mimics the effect of tumor-promoting phorbol diesters to inhibit the high-affinity binding of '25I-labeled epidermal growth factor (125I-EGF). PDGF, like phorbol.diesters, was found to increase the phosphorylation state of EGF receptors immunoprecipitated from intact fibroblasts that were labeled to equilibrium with (32liphosphate. Phosphoamino acid analysis of the EGF receptors indicated that both PDGF and phorbol diesters increased the level of [32P~phosphoserine and [32P~phosphothreonine. Phosphopeptide mapping of the EGF receptor demonstrated that PDGF increased the phosphorylation of several sites and induced the phosphorylation of a site that was not observed to be phosphorylated on EGF receptors isolated from control cells. This latter phosphorylation site on the EGF receptor was identified as threonine-654, previously shown to be phosphorylated in response to phorbol diesters in intact cells or by purified protein kinase C in vitro. Further, it was observed that PDGF mimicked the action of phorbol diesters to inhibit the EGF-dependent tyrosine phosphorylation of the EGF receptor in [32Pjphosphate-labeled fibroblasts.These results are consistent with the hypothesis that increases in diacylglycerol and Ca2' levels caused by addition of PDGF to fibroblasts activate protein kinase C and that this kinase, at least in part, mediates the effect of PDGF on the phosphorylation of the EGF receptor. The data further suggest that protein kinase C may play an important role in the regulation of cellular metabolism and proliferation by PDGF.Platelet-derived growth factor (PDGF) is a potent polypeptide mitogen that is released into the blood during platelet lysis after tissue injury. The full mitogenic effect of PDGF is only expressed in the presence of other growth factors such as epidermal growth factor (EGF) and insulin (1). Interestingly, this effect is also characteristic of tumor-promoting phorbol diesters such as 4p-phorbol 12/3-myristate 13a-acetate (PMA), which stimulate the growth of quiescent fibroblasts synergistically with EGF and insulin (2, 3). An-other striking similarity between the actions of PDGF and phorbol diesters is a rapid inhibition of 125I-labeled EGF (125I-EGF) binding to the receptors ofcultured cells (4-12). In view of the similarity of these actions of PDGF and PMA on the EGF receptor, we considered the possibility that these two agents may have a similar mechanism of action.It has been reported that PMA causes the phosphorylation of the EGF receptor on senine and threonine residues, and it has been suggested that this phosphorylation is causally related to the effect of PMA on the EGF receptor (13)(14)(15). Phosphopeptide mapping of the EGF receptor has revealed that the phosphorylation state of several sites is increased after treatment of cells with phorbol diester (13,15,16). One of these sites was observed to be uniquely phosphorylated on the EGF receptor isolated from PMA-trea...

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supporting

confidence: 78%

mentioning

confidence: 99%

Platelet-derived growth factor mimics phorbol diester action on epidermal growth factor receptor phosphorylation at threonine-654.

Davis¹,

Czech²

1985

Proc. Natl. Acad. Sci. U.S.A.

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“…The EGF receptor is negatively modulated by a mechanism mediated by PKC and activated by PDGF and bombesin (3,5,9,36,37). We have shown that an analogous feedback mechanism appears to be triggered also by EGF itself, through the activation of PKC.…”

Section: Kinetics Of Tyrosine Phosphorylation Of Egf Receptor P-tyrmentioning

confidence: 86%

Kinetics and regulation of the tyrosine phosphorylation of epidermal growth factor receptor in intact A431 cells.

Sturani¹,

Zippel²,

Toschi³

et al. 1988

Mol. Cell. Biol.

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We have previously reported that antibodies to phosphotyrosine recognize the phosphorylated forms of platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) receptors (Zippel et al., Biochim. Biophys. Acta 881:54-61, 1986, and Sturani et al., Biochem. Biophys. Res. Commun. 137:343-350, 1986 The epidermal growth factor (EGF) receptor (26) is a transmembrane protein which contains the EGF-binding domain in its extracellular N-terminal region and a protein kinase domain in the intracellular portion (2, 32). Near the carboxy terminus, there are tyrosine residues which are specifically phosphorylated by the autokinase activity (13). When intact cells are exposed to EGF, autophosphorylation occurs primarily on tyrosine 1173. The significance of this self-phosphorylation has been debated (4, 14) and it has been suggested that it increases the tyrosine kinase activity toward other substrates (4).The EGF receptor is also a substrate of protein kinase C (PKC); addition of tumor promoters or of physiological activators of PKC to intact cells induces receptor phosphorylation on several serine and threonine residues, inhibits high-affinity binding of EGF, and reduces the protein kinase activity of the receptor (8,12,16,20). Moreover, it has recently been observed that EGF promotes the phosphorylation of the threonine 654 of its own receptor (22, 34), so that the possible role of PKC in homologous feedback regulation of EGF receptor has been suggested.The human carcinoma cell line A431 bears an unusually high number of EGF receptors, and it is largely used for studying their biochemistry and regulation (11,18,19,23,31). We report a study on kinetic and regulatory aspects of the tyrosine phosphorylation of EGF receptor in intact A431 cells. The tyrosine phosphorylation of the receptor has been studied by using azobenzyl phosphonate antibodies that specifically cross-react with phosphotyrosine (P-tyr) (10, * Corresponding author. 25). We have previously shown that these antibodies are a sensitive tool for detecting and quantitatively evaluating the tyrosine-phosphorylated form of platelet-derived growth factor (PDGF) (29, 38) and EGF receptors (30) in Western blots (immunoblots) of total cellular extracts. We have now determined the fraction of total EGF receptors phosphorylated on tyrosine and the cellular localization of the phosphorylated receptor molecules. Moreover, we have analyzed the conditions affecting receptor phosphorylation and dephosphorylation in intact A431 cells stimulated by EGF

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“…Platelet-derived growth factor can also act by modulating other growth factors. For example, in the 3T3 cell system, PDGF modulates EGF receptor by inducing a transient loss of EGF binding activity, independently of any change in EGF receptor affinity [258]. In serumcontaining medium, FGF was shown to decrease the differentiation of TA1 cells [166,167].…”

Section: Other Growth Factors and Cytokinesmentioning

confidence: 99%

The adipose conversion process: regulation by extracellular and intracellular factors

Boone

Mourot

Gregoire³

et al. 2000

Reprod. Nutr. Dev.

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-White adipose tissue regulates lipid metabolism and acts as a secretory organ. Because of its importance for human health and animal production, many studies have attempted to better understand its development at the cellular and molecular levels by culturing preadipose cells in vitro. This synthesis article describes our current knowledge, acquired by this approach, concerning the regulation of the different steps of the adipocyte differentiation program by extracellular (hormones, cytokines, growth factors, retinoids and fatty acids) and intracellular agents (second messengers and transcription factors). The discrepant effects that have been observed for some of these factors are also discussed. This information is very important in the perspective of a better control of fat deposits in human and breeding species.preadipocyte / differentiation / hormonal agent / second messenger / transcription factor Résumé -Le processus d'adipoconversion : sa régulation par des facteurs extracellulaires et intracellulaires. Le tissu adipeux blanc régule le métabolisme lipidique et agit comme un organe de sécrétion. Étant donné son importance pour la santé humaine et la production animale, de nombreuses études ont tenté de mieux comprendre son développement aux niveaux cellulaire et moléculaire en utilisant des cultures de préadipocytes. Cet article de synthèse décrit notre connaissance actuelle, issue de cette approche, concernant la régulation des différentes étapes du programme de la diffé-renciation adipocytaire par des facteurs extracellulaires (hormones, cytokines, facteurs de croissance, rétinoïdes et acides gras) et intracellulaires (seconds messagers et facteurs de transcription). Les effets divergents observés pour certains de ces facteurs sont également discutés. Ces informations sont très importantes dans la perspective d'un meilleur contrôle des dépôts adipeux chez l'humain et les espèces d'élevage.préadipocyte / différenciation / hormone / second messager / facteur de transcription Reprod. Nutr. Dev. 40 (2000) 325-358 325

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Modulation of Epidermal Growth Factor Receptors on 3T3 Cells by Platelet-Derived Growth Factor

Cited by 180 publications

References 20 publications

Platelet-derived growth factor mimics phorbol diester action on epidermal growth factor receptor phosphorylation at threonine-654.

Platelet-derived growth factor mimics phorbol diester action on epidermal growth factor receptor phosphorylation at threonine-654.

Kinetics and regulation of the tyrosine phosphorylation of epidermal growth factor receptor in intact A431 cells.

The adipose conversion process: regulation by extracellular and intracellular factors

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