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

Transmembrane adaptor proteins (TRAPs) are important organizers and regulators of immunoreceptor-mediated signaling. A bioinformatic search revealed several potential novel TRAPs, including a highly conserved protein, proline rich 7 (PRR7), previously described as a component of the PSD-95/N-methyl-d-aspartate receptor protein complex in postsynaptic densities (PSD) of rat neurons. Our data demonstrate that PRR7 is weakly expressed in other tissues but is readily up-regulated in activated human peripheral blood lymphocytes. Transient overexpression of PRR7 in Jurkat T cell line led to gradual apoptotic death dependent on the WW domain binding motif surrounding Tyr-166 in the intracellular part of PRR7. To circumvent the pro-apoptotic effect of PRR7, we generated Jurkat clones with inducible expression of PRR7 (J-iPRR7). In these cells acute induction of PRR7 expression had a dual effect. It resulted in up-regulation of the transcription factor c-Jun and the activation marker CD69 as well as enhanced production of IL-2 after phorbol 12-myristate 13-acetate (PMA) and ionomycin treatment. On the other hand, expression of PRR7 inhibited general tyrosine phosphorylation and calcium influx after T cell receptor cross-linking by antibodies. Moreover, we found PRR7 constitutively tyrosine-phosphorylated and associated with Src. Collectively, these data indicate that PRR7 is a potential regulator of signaling and apoptosis in activated T cells.

• MeSH
• Adaptor Proteins, Signal Transducing biosynthesis   genetics   immunology   MeSH
• Amino Acid Motifs MeSH
• Apoptosis drug effects   physiology   MeSH
• Caco-2 Cells MeSH
• Antigens, CD biosynthesis   genetics   immunology   MeSH
• Antigens, Differentiation, T-Lymphocyte biosynthesis   genetics   immunology   MeSH
• Phosphorylation drug effects   physiology   MeSH
• HEK293 Cells MeSH
• Interleukin-2 biosynthesis   genetics   immunology   MeSH
• Ionophores pharmacology   MeSH
• Ionomycin pharmacology   MeSH
• Jurkat Cells MeSH
• Carcinogens pharmacology   MeSH
• Rats MeSH
• Lectins, C-Type biosynthesis   genetics   immunology   MeSH
• Humans MeSH
• Proto-Oncogene Proteins c-jun genetics   immunology   metabolism   MeSH
• Receptors, Antigen, T-Cell genetics   immunology   metabolism   MeSH
• Gene Expression Regulation physiology   MeSH
• T-Lymphocytes immunology   metabolism   MeSH
• Protein Structure, Tertiary MeSH
• Tetradecanoylphorbol Acetate pharmacology   MeSH
• U937 Cells MeSH
• Calcium Signaling drug effects   physiology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adaptor Proteins, Signal Transducing MeSH
• Antigens, CD MeSH
• CD69 antigen MeSH Browser
• Antigens, Differentiation, T-Lymphocyte MeSH
• IL2 protein, human MeSH Browser
• Interleukin-2 MeSH
• Ionophores MeSH
• Ionomycin MeSH
• Carcinogens MeSH
• Lectins, C-Type MeSH
• Proto-Oncogene Proteins c-jun MeSH
• Receptors, Antigen, T-Cell MeSH
• Tetradecanoylphorbol Acetate MeSH