Role of lipid domains in egf receptor signaling

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Epidermal growth factor (EGF), a 53 amino acid polypeptide, elicits its cellular effects through binding to the cell surface EGF receptor. The EGF receptor is a transmembrane tyrosine kinase composed of an α620 amino acid extracellular ligand binding domain, a single-pass transmembrane domain, a tyrosine kinase domain, and an α200 amino acid C-terminal tail. The EGF receptor is a member of the ErbB receptor family having four members that include the EGF receptor (ErbB1), HER2/neu (ErbB2), ErbB3, and ErbB4. The receptors are structurally similar but in ErbB3 the kinase domain is inactive. The ErbB receptors bind a family of ligands, with each receptor having different ligand selectivity. ErbB2 is the exception, in that there is no known ligand for this receptor. The EGF receptor, upon binding ligand, dimerizes and undergoes inter-chain autophosphorylation, primarily in the C-terminal tail of the receptor. This promotes complex formation with SH2 and PTB domain-containing proteins and initiates intracellular downstream signaling cascades. The effect of cholesterol on EGF receptor kinase activity is traceable to its effect on the ability of EGF to induce receptor dimer formation. Cholesterol depletion enhances receptor dimerization, whereas cholesterol loading impairs dimerization. Overexpression of the wild-type EGF receptor or a C-terminally truncated form of the EGF receptor results in an EGF-dependent tyrosine phosphorylation of caveolin-1 that seems to be mediated by pp60src. EGF induces the redistribution of caveolin-1 from the plasma membrane to an early endocytic compartment. The observation that EGF stimulates the phosphorylation and endocytosis of phospholipid scramblase 1, a resident lipid raft protein, is consistent with the notion that EGF may regulate the trafficking of a variety of proteins present in low-density membrane domains.

Original languageEnglish
Title of host publicationHandbook of Cell Signaling, 2/e
PublisherElsevier Inc.
Number of pages6
ISBN (Print)9780123741455
StatePublished - Dec 1 2010

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    Pike, L. J. (2010). Role of lipid domains in egf receptor signaling. In Handbook of Cell Signaling, 2/e (Vol. 1, pp. 359-364). Elsevier Inc..