title: SCIMP, a transmembrane adaptor protein involved in major histocompatibility complex class II signaling.
abstract: Formation of the immunological synapse between an antigen-presenting cell (APC) and a T cell leads to signal generation in both cells involved. In T cells, the lipid raft-associated transmembrane adaptor protein LAT plays a central role. Its phosphorylation is a crucial step in signal propagation, including the calcium response and mitogen-activated protein kinase activation, and largely depends on its association with the SLP76 adaptor protein. Here we report the discovery of a new palmitoylated transmembrane adaptor protein, termed SCIMP. SCIMP is expressed in B cells and other professional APCs and is localized in the immunological synapse due to its association with tetraspanin-enriched microdomains. In B cells, it is constitutively associated with Lyn kinase and becomes tyrosine phosphorylated after major histocompatibility complex type II (MHC-II) stimulation. When phosphorylated, SCIMP binds to the SLP65 adaptor protein and also to the inhibitory kinase Csk. While the association with SLP65 initiates the downstream signaling cascades, Csk binding functions as a negative regulatory loop. The results suggest that SCIMP is involved in signal transduction after MHC-II stimulation and therefore serves as a regulator of antigen presentation and other APC functions.
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague 14220, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Draber
authors.forename: Ivana
authors.initials: I
authors.lastname: Vonkova
authors.forename: Ondrej
authors.initials: O
authors.lastname: Stepanek
authors.forename: Matous
authors.initials: M
authors.lastname: Hrdinka
authors.forename: Marketa
authors.initials: M
authors.lastname: Kucova
authors.forename: Tereza
authors.initials: T
authors.lastname: Skopcova
authors.forename: Pavel
authors.initials: P
authors.lastname: Otahal
authors.forename: Pavla
authors.initials: P
authors.lastname: Angelisova
authors.forename: Vaclav
authors.initials: V
authors.lastname: Horejsi
authors.forename: Mandy
authors.initials: M
authors.lastname: Yeung
authors.forename: Arthur
authors.initials: A
authors.lastname: Weiss
authors.forename: Tomas
authors.initials: T
authors.lastname: Brdicka
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D000081247:CSK Tyrosine-Protein Kinase; D057809:HEK293 Cells; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D054992:Immunological Synapses / Q000737:chemistry; D008213:Lymphocyte Activation; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D018909:src Homology Domains; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; C568696:SCIMP protein, human; C092947:SLP-76 signal Transducing adaptor proteins; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D020928:Mitogen-Activated Protein Kinases