title: Phosphorylation of c-Cbl protooncogene product following ethanol administration in rat cerebellum: possible involvement of Fyn kinase.
abstract: We have previously shown that ethanol administration results in tyrosine phosphorylation of the 130 kDa protein in rat brain, and identified the protein as Cas, the crk-associated src substrate. In the present study, we demonstrate that Cbl of a 120 kDa protein is also tyrosine-phosphorylated in the cerebellum in response to ethanol administration. We also investigated whether Fyn kinase was involved in ethanol-induced Cbl phosphorylation. Immunoprecipitation experiments showed that the amount of coimmunoprecipitated Fyn kinase with an anti-Cbl antibody increased in extracts from ethanol-administered rats compared to those from saline-administered rats. Exogenous Fyn kinase was shown to phosphorylate on tyrosine residue(s) of Cbl from the cerebellum in vitro. Furthermore, Fyn kinase and Cbl were demonstrated immunohistochemically to be coexpressed in white matter in the cerebellum. These findings indicate that Cbl is tyrosine-phosphorylated in rat cerebellum in response to ethanol administration, and also raise the possibility that Fyn kinase may be involved in the process.
authors.affiliation: Department of Legal Medicine, Osaka Medical College, 2-7 Daigaku, 569-8686, Takatsuki, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Nishio
authors.forename: Mami
authors.initials: M
authors.lastname: Otsuka
authors.forename: Shinya
authors.initials: S
authors.lastname: Kinoshita
authors.forename: Takahito
authors.initials: T
authors.lastname: Tokuoka
authors.forename: Miwa
authors.initials: M
authors.lastname: Nakajima
authors.forename: Yoshika
authors.initials: Y
authors.lastname: Noda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fukuyama
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000494:pharmacology; D050721:Proto-Oncogene Proteins c-cbl; D051076:Proto-Oncogene Proteins c-fyn; D051381:Rats; D017207:Rats, Sprague-Dawley; D044767:Ubiquitin-Protein Ligases
chemical_list: D011518:Proto-Oncogene Proteins; D000431:Ethanol; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; C494961:Fyn protein, rat; D051076:Proto-Oncogene Proteins c-fyn