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TOM1L1 Is a Lyn Substrate Involved in Fc{epsilon}RI Signaling in Mast Cells.

TOM1L1 Is a Lyn Substrate Involved in Fc{epsilon}RI Signaling in Mast Cells. Research Abstract Details 

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  • TOM1L1 Is a Lyn Substrate Involved in Fc{epsilon}RI Signaling in Mast Cells. Abstract Text:

    juan zhangJuan Zhang,katsuhiro suzukiKatsuhiro Suzuki,tomohiro hitomiTomohiro Hitomi,reuben p siraganianReuben P Siraganian,juan zhangJuan Zhang,katsuhiro suzukiKatsuhiro Suzuki,tomohiro hitomiTomohiro Hitomi,reuben p siraganianReuben P Siraganian,

    Protein-tyrosine kinase Lyn and Syk are critical for antigen-receptor-induced signal transduction in mast cells. To identify novel Lyn/Syk substrates, we screened an RBL-2H3 bacterial expression library for proteins that were tyrosine phosphorylated with baculoviral expressed Lyn or Syk. Five clones as potential Lyn substrates and eight clones as Syk substrates were identified including known substrates such as SLP-76, LAT, and alpha-tubulin. A potential substrate of Lyn identified was the molecule TOM1L1, which has several domains thought to be important for membrane trafficking and protein-protein interactions. Because the function of TOM1L1 is unclear, the rat TOM1L1 full-length cDNA was isolated and used to express the protein in COS-1 and RBL-2H3 mast cells. In COS-1 cells, the co-transfection of TOM1L1 and Lyn, but not Syk, resulted in the tyrosine phosphorylation of TOM1L1. In RBL-2H3 mast cells, the overexpressed TOM1L1 was strongly tyrosine phosphorylated in non-stimulated cells, and this phosphorylation was enhanced by FcepsilonRI aggregation. By subcellular fractionation, wild-type TOM1L1 was mainly in the cytoplasm with a small fraction constitutively associated with the membrane; this association was markedly reduced in deletion mutants lacking several of the protein interaction domains. The overexpression of TOM1L1 enhanced antigen-induced tumor necrosis factor (TNF) alpha generation and release. Both protein interaction domains (VHS and the coiled-coil domains) were required for the increased TNFalpha release, but not the increased TNFalpha generation. These results suggest that TOM1L1 is a novel protein involved in the FcepsilonRI signal transduction for the generation of cytokines.

    TOM1L1 Is a Lyn Substrate Involved in Fc{epsilon}RI Signaling in Mast Cells. Publishing Authors By Initials

    j zhangJ Zhang,k suzukiK Suzuki,t hitomiT Hitomi,rp siraganianRP Siraganian,j zhangJ Zhang,k suzukiK Suzuki,t hitomiT Hitomi,rp siraganianRP Siraganian,

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    TOM1L1 Is a Lyn Substrate Involved in Fc{epsilon}RI Signaling in Mast Cells. Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: The Journal of biological chemistry

    VOLUME: 282

    Page Numbers: 37669-77

    Journal Abbreviation: J. Biol. Chem.

    ISSN: 0021-9258

    DAY: 31

    MONTH: 10

    YEAR: 2007

    TOM1L1 Is a Lyn Substrate Involved in Fc{epsilon}RI Signaling in Mast Cells. Information

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    LANGUAGE: eng

    NlmUniqueID: 2985121

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    Grant and Affiliation Information for TOM1L1 Is a Lyn Substrate Involved in Fc{epsilon}RI Signaling in Mast Cells.

    AFFILIATION: Receptors and Signal Transduction Section, Oral Infection and Immunity Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892.

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: J Biol Chem

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