title: APS-mediated ubiquitination of the insulin receptor enhances its internalization, but does not induce its degradation.
abstract: APS, a tyrosine kinase adaptor protein with pleckstrin homology and Src homology 2 domains, is rapidly and strongly tyrosine-phosphorylated by insulin receptor kinase upon insulin stimulation. We have previously shown that APS knockout mice have increased insulin sensitivity, and that this enhancement is possibly due to increased insulin-response on adipose tissues. However, the function of APS in insulin signaling has so far been controversial. Here, we report that APS enhanced ligand-dependent multi-ubiquitination of the insulin receptor (IR) in CHO cells overexpressing the IR. APS-mediated ubiquitination of the IR induced enhancement of the IR internalization, but did not affect the IR degradation. This finding shows one of the pleiotropic functions of APS in insulin signaling.
authors.affiliation: Division of Molecular Genetics, Institute for Enzyme Research, The University of Tokushima, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kishi
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Mawatari
authors.forename: Kikuko
authors.initials: K
authors.lastname: Sakai-Wakamatsu
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yuasa
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.forename: Makoto
authors.initials: M
authors.lastname: Ogura-Sawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakaya
authors.forename: Shigetsugu
authors.initials: S
authors.lastname: Hatakeyama
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Ebina
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007328:Insulin / Q000378:metabolism; D051379:Mice; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007328:Insulin; C488161:Sh2b2 protein, mouse; D025801:Ubiquitin; D011972:Receptor, Insulin