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.
Highlights
LST1/A was a poorly characterized protein encoded in the MHCIII locus
We show that LST1/A, an incompletely characterized protein encoded by MHCIII locus, is a palmitoylated transmembrane adaptor protein
LST1/A Is Transmembrane Adaptor Protein Containing immunoreceptor tyrosine-based inhibitory motif (ITIM) and ITIM-like Motifs—LST1/A was identified as a potential transmembrane adaptor proteins (TRAPs) during our human genome-wide in silico screen described previously [10]
Summary
LST1/A was a poorly characterized protein encoded in the MHCIII locus. Results: LST1/A is a myeloid cell-specific transmembrane adaptor associated with the tetraspanin-enriched microdomains that inhibits signaling by recruiting the protein tyrosine phosphatases SHP-1/SHP-2. We show that LST1/A, an incompletely characterized protein encoded by MHCIII locus, is a palmitoylated transmembrane adaptor protein It is expressed in leukocytes of the myeloid lineage, where it localizes to the tetraspanin-enriched microdomains. Several studies reported enrichment or specific expression of LST1 in leukocytes or leukocyte-rich tissues [1, 3, 7], whereas others indicated that the expression of LST1 is relatively ubiquitous [5, 8] It seems that production of particular isoforms could be differentially regulated, which further complicates expression analysis [5, 9]. We thoroughly characterize the LST1/A isoform with the emphasis on bioinformatic analysis of its amino acid sequence, expression profile, biochemical characterization, and binding partners Based on these data, we propose a role for LST1/A in negative regulation of cellular signaling
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