title: Human tumorous imaginal disc 1 (TID1) associates with Trk receptor tyrosine kinases and regulates neurite outgrowth in nnr5-TrkA cells.
abstract: The human tumorous imaginal disc 1 (TID1) proteins including TID1(L) and TID1(S), members of the DnaJ domain protein family, are involved in multiple intracellular signaling pathways such as apoptosis induction, cell proliferation, and survival. Here we report that TID1 associates with the Trk receptor tyrosine kinases and regulates nerve growth factor (NGF)-induced neurite outgrowth in PC12-derived nnr5 cells. Binding assays and transfection studies showed that the carboxyl-terminal end of TID1 (residues 224-429) bound to Trk at the activation loop (Tyr(P)(683)-Tyr(684)(P)(684) in rat TrkA) and that TID1 was tyrosine phosphorylated by Trk both in yeast and in transfected cells. Moreover endogenous TID1 was also tyrosine phosphorylated by and co-immunoprecipitated with Trk in neurotrophin-stimulated primary rat hippocampal neurons. Overexpression studies showed that both TID1(L) and TID1(S) significantly facilitated NGF-induced neurite outgrowth in TrkA-expressing nnr5 cells possibly through a mechanism involving increased activation of mitogen-activated protein kinase. Consistently knockdown of endogenous TID1, mediated with specific short hairpin RNA, significantly reduced NGF-induced neurite growth in nnr5-TrkA cells. These data provide the first evidence that TID1 is a novel intracellular adaptor that interacts with the Trk receptor tyrosine kinases in an activity-dependent manner to facilitate Trk-dependent intracellular signaling.
authors.affiliation: Cell Biology Group, Robarts Research Institute, London, Ontario, Canada.
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Liu
authors.forename: James I S
authors.initials: JI
authors.lastname: MacDonald
authors.forename: Todd
authors.initials: T
authors.lastname: Hryciw
authors.forename: Chunhui
authors.initials: C
authors.lastname: Li
authors.forename: Susan O
authors.initials: SO
authors.lastname: Meakin
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000235:genetics; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D016716:PC12 Cells; D010766:Phosphorylation; D034622:RNA Interference; D051381:Rats; D020917:Receptor, trkA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D020798:Two-Hybrid System Techniques; D014443:Tyrosine / Q000737:chemistry
chemical_list: C120664:DNAJA3 protein, human; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D011994:Recombinant Proteins; D014443:Tyrosine; D004247:DNA; D020917:Receptor, trkA