title: Fyn binds to and phosphorylates T cell immunoglobulin and mucin domain-1 (Tim-1).
abstract: The gene encoding T cell immunoglobulin and mucin domain-1 (Tim-1) is linked to atopy and asthma susceptibility in mice and humans. Tim-1 is a transmembrane protein expressed on activated lymphocytes and appears to have a role as a co-stimulatory receptor in T cells. The protein has not been shown to have enzymatic activity but contains a site within its cytoplasmic tail predicted to be a target for tyrosine kinases. Here, we show that Tim-1 can associate with the kinase Fyn, a member of the Src family of tyrosine kinases. This association does not require Fyn's kinase activity and is independent of the phosphorylation of a conserved tyrosine present within the cytoplasmic tail of Tim-1. Fyn is necessary for phosphorylation of this tyrosine in Tim-1 and the phosphorylation of Tim-1 varies with the levels of Fyn present in cells. These data suggest a role for Fyn in the signaling downstream of Tim-1.
authors.affiliation: Department of Internal Medicine, University of Iowa Carver College of Medicine. 200 Hawkins Drive, Iowa City, IA 52242, USA. miranda-curtiss@uiowa.edu
authors.forename: Miranda L
authors.initials: ML
authors.lastname: Curtiss
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Hostager
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Stepniak
authors.forename: Melody
authors.initials: M
authors.lastname: Singh
authors.forename: Natalie
authors.initials: N
authors.lastname: Manhica
authors.forename: Judit
authors.initials: J
authors.lastname: Knisz
authors.forename: Geri
authors.initials: G
authors.lastname: Traver
authors.forename: Paul D
authors.initials: PD
authors.lastname: Rennert
authors.forename: John D
authors.initials: JD
authors.lastname: Colgan
authors.forename: Paul B
authors.initials: PB
authors.lastname: Rothman
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D011991:Receptors, Virus; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn