title: LST1/A is a myeloid leukocyte-specific transmembrane adaptor protein recruiting protein tyrosine phosphatases SHP-1 and SHP-2 to the plasma membrane.
abstract: Transmembrane adaptor proteins are membrane-anchored proteins consisting of a short extracellular part, a transmembrane domain, and a cytoplasmic part with various protein-protein interaction motifs but lacking any enzymatic activity. They participate in the regulation of various signaling pathways by recruiting other proteins to the proximity of cellular membranes where the signaling is often initiated and propagated. In this work, we show that LST1/A, an incompletely characterized protein encoded by MHCIII locus, is a palmitoylated transmembrane adaptor protein. It is expressed specifically in leukocytes of the myeloid lineage, where it localizes to the tetraspanin-enriched microdomains. In addition, it binds SHP-1 and SHP-2 phosphatases in a phosphotyrosine-dependent manner, facilitating their recruitment to the plasma membrane. These data suggest a role for LST1/A in negative regulation of signal propagation.
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 142 20 Prague, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Draber
authors.forename: Ondrej
authors.initials: O
authors.lastname: Stepanek
authors.forename: Matous
authors.initials: M
authors.lastname: Hrdinka
authors.forename: Ales
authors.initials: A
authors.lastname: Drobek
authors.forename: Lukas
authors.initials: L
authors.lastname: Chmatal
authors.forename: Linda
authors.initials: L
authors.lastname: Mala
authors.forename: Tereza
authors.initials: T
authors.lastname: Ormsby
authors.forename: Pavla
authors.initials: P
authors.lastname: Angelisova
authors.forename: Vaclav
authors.initials: V
authors.lastname: Horejsi
authors.forename: Tomas
authors.initials: T
authors.lastname: Brdicka
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D008285:Major Histocompatibility Complex / Q000502:physiology; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism*; D051179:Plakins / Q000378:metabolism; D061251:Primary Cell Culture; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D020298:U937 Cells
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C093604:LST1 protein, human; D008565:Membrane Proteins; D051179:Plakins; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6