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.

• MeSH
• Cell Membrane metabolism   MeSH
• HEK293 Cells MeSH
• HeLa Cells MeSH
• Major Histocompatibility Complex physiology   MeSH
• Intracellular Signaling Peptides and Proteins MeSH
• Jurkat Cells MeSH
• Humans MeSH
• Membrane Proteins chemistry   genetics   metabolism   MeSH
• Molecular Sequence Data MeSH
• Myeloid Cells cytology   metabolism   MeSH
• Plakins metabolism   MeSH
• Primary Cell Culture MeSH
• Pseudopodia metabolism   MeSH
• Amino Acid Sequence MeSH
• Signal Transduction physiology   MeSH
• Protein Structure, Tertiary physiology   MeSH
• Protein Transport physiology   MeSH
• Protein Tyrosine Phosphatase, Non-Receptor Type 11 metabolism   MeSH
• Protein Tyrosine Phosphatase, Non-Receptor Type 6 metabolism   MeSH
• U937 Cells MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Intracellular Signaling Peptides and Proteins MeSH
• LST1 protein, human MeSH Browser
• Membrane Proteins MeSH
• Plakins MeSH
• PTPN11 protein, human MeSH Browser
• PTPN6 protein, human MeSH Browser
• Protein Tyrosine Phosphatase, Non-Receptor Type 11 MeSH
• Protein Tyrosine Phosphatase, Non-Receptor Type 6 MeSH

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.

• MeSH
• Adaptor Proteins, Signal Transducing chemistry   metabolism   MeSH
• Lymphocyte Activation MeSH
• Antigen-Presenting Cells immunology   MeSH
• B-Lymphocytes immunology   metabolism   MeSH
• CSK Tyrosine-Protein Kinase MeSH
• Phosphoproteins metabolism   MeSH
• HEK293 Cells MeSH
• Immunological Synapses chemistry   MeSH
• Humans MeSH
• RNA, Small Interfering MeSH
• Membrane Microdomains chemistry   metabolism   MeSH
• Membrane Proteins chemistry   genetics   immunology   metabolism   MeSH
• Histocompatibility Antigens Class II immunology   metabolism   MeSH
• Mitogen-Activated Protein Kinases metabolism   MeSH
• Molecular Sequence Data MeSH
• Antigen Presentation MeSH
• RNA Interference MeSH
• Amino Acid Sequence MeSH
• Signal Transduction MeSH
• src-Family Kinases metabolism   MeSH
• src Homology Domains MeSH
• T-Lymphocytes immunology   MeSH
• Protein-Tyrosine Kinases chemistry   metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adaptor Proteins, Signal Transducing MeSH
• B cell linker protein MeSH Browser
• CSK Tyrosine-Protein Kinase MeSH
• CSK protein, human MeSH Browser
• Phosphoproteins MeSH
• lyn protein-tyrosine kinase MeSH Browser
• RNA, Small Interfering MeSH
• Membrane Proteins MeSH
• Histocompatibility Antigens Class II MeSH
• Mitogen-Activated Protein Kinases MeSH
• SCIMP protein, human MeSH Browser
• src-Family Kinases MeSH
• SLP-76 signal Transducing adaptor proteins MeSH Browser
• Protein-Tyrosine Kinases MeSH