RGD Reference Report - Epidermal growth factor induction of phenotype-dependent cell cycle arrest in vascular smooth muscle cells is through the mitogen-activated protein kinase pathway. - Rat Genome Database

RGD Reference Report - Epidermal growth factor induction of phenotype-dependent cell cycle arrest in vascular smooth muscle cells is through the mitogen-activated protein kinase pathway. - Rat Genome Database

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Epidermal growth factor induction of phenotype-dependent cell cycle arrest in vascular smooth muscle cells is through the mitogen-activated protein kinase pathway.
Authors:	Gui, Y Zheng, XL
Citation:	Gui Y and Zheng XL, J Biol Chem. 2003 Dec 26;278(52):53017-25. Epub 2003 Oct 9.
RGD ID:	1581912
Pubmed:	PMID:14551192 (View Abstract at PubMed)
DOI:	DOI:10.1074/jbc.M309640200 (Journal Full-text)
The heterogeneity of vascular smooth muscle cells is well established in tissue culture, but their differential responses to growth factors are not completely defined. We wished to identify effects of epidermal growth factor (EGF) on vascular smooth muscle cells in distinct phenotypes, such as spindle and epithelioid. We found that the EGF receptors were abundant in epithelioid cells but not spindle cells. EGF treatment inhibited serum-independent DNA synthesis, which was absent in spindle cells, of epithelioid cells. Additionally, using a pulse-chase assay, we found that bromodeoxyuridine-labeled cells failed to re-enter the S phase in the presence of EGF. These EGF effects were abolished by either inhibiting the EGF receptor tyrosine kinase with AG1478 or inhibiting the mitogen-activated protein kinase pathway with PD98059. In response to treatment with EGF, the EGF receptor was phosphorylated, which was correlated with phosphorylation and activation of p42/44 mitogen-activated protein kinases. Inhibition of EGF receptor phosphorylation and mitogen-activated protein kinase activation resulted in a reversal of the EGF-induced inhibition of bromodeoxyuridine incorporation and cell cycle arrest. Subsequent studies revealed that the activation of the EGF receptor and the mitogen-activated protein kinase pathway in epithelioid cells induced expression of the cell cycle inhibitory protein p27Kip1 but not p21Cip1. Taken together, our data demonstrate that the EGF receptor is abundantly expressed in epithelioid vascular smooth muscle cells and that the activation of this receptor results in cell cycle arrest through activation of the mitogen-activated protein kinase pathway.

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Biological Process

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
negative regulation of mitotic cell cycle		IMP		1581912		RGD
positive regulation of MAPK cascade		IMP		1581912		RGD

Objects Annotated

Genes (Rattus norvegicus)

Egfr (epidermal growth factor receptor)

Objects referenced in this article

Gene	EGFR	epidermal growth factor receptor	Homo sapiens
Gene	Egfr	epidermal growth factor receptor	Mus musculus

Additional Information