title: Desensitization by different strategies of epidermal growth factor receptor and ErbB4.
abstract: Four transmembrane tyrosine kinases constitute the ErbB protein family: epidermal growth factor receptor (EGFR) or ErbB1, ErbB2, ErbB3, and ErbB4. In general, the structure and mechanism of the activation of these members are similar. However, significant differences in homologous desensitization are known between EGFR and ErbB4. Desensitization of ligand-occupied EGFR occurs by endocytosis, while that of ErbB4 occurs by selective cleavage at the cell surface. Because ErbB4 is abundantly expressed in neurons from fetal to adult brains, elucidation of the desensitization mechanism is important to understand neuronal development and synaptic functions. Recently, it has become clear that heterologous desensitization of EGFR and ErbB4 are induced by endocytosis and cleavage, respectively, similar to homologous desensitization. It has been reported that heterologous desensitization of EGFR is induced by serine phosphorylation of EGFR via the p38 mitogen-activated protein kinase (p38 MAP kinase) pathway in various cell lines, including alveolar epithelial cells. In contrast, the protein kinase C pathway is involved in ErbB4 cleavage. In this review, we will describe recent advances in the desensitization mechanisms of EGFR and ErbB4, mainly in alveolar epithelial cells and hypothalamic neurons, respectively.
authors.affiliation: Department of Biochemistry, Graduate School of Medicine, University of the Ryukyus, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Sayomi
authors.initials: S
authors.lastname: Higa-Nakamine
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Noguchi
authors.forename: Noriko
authors.initials: N
authors.lastname: Maeda
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kondo
authors.forename: Seikichi
authors.initials: S
authors.lastname: Toku
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kukita
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sugahara
mesh_terms: D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005408:Flagellin / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism; D066247:Receptor, ErbB-4; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D014409:Tumor Necrosis Factor-alpha; D005408:Flagellin; D007987:Gonadotropin-Releasing Hormone; D012694:Serine; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4; D011493:Protein Kinase C