|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
T Cell, Mature
|75 / 80|
|SLP-76 is a cytosolic adaptor protein expressed on several cell types of hematopoietic origin. SLP-76 associates with other molecules and is required for coupling receptor ligation with more distal signaling events on immature thymocytes, mature T cells, platelets, mast cells, macrophages, NK cells, and megakaryocytes. SLP-76 is not expressed on murine B cells. Expression is regulated during thymocyte development. The expression increases following activation on mature T cells and remains elevated on the memory cell subset. |
| MOLECULAR FAMILY NAME: slp-76 family -->adaptor proteins.|
SLP-76 names: SH2 domain-containing leukocyte protein of 76kD (spl-76), lymphocyte cytosolic protein 2 (LCP2), 76-kDa phosphoprotein (pp76), and 76-kDa Vav-associated protein.
SLP-76 was originally identified as a substrate of the ZAP-70 protein tyrosine kinase following TCR ligation in the leukemic T cell line Jurkat. Human and murine SLP-76 cDNAs encode 533 aa proteins that are 72% identical and are comprised of 3 major modular domains that regulate protein interactions. The NH2-terminus contains an acidic- domain that harbors several tyrosine-residues that are phosphorylated following TCR ligation. The acidic-region also contains 1 PEST domain. The central portion of SLP-76 is rich in proline-residues. There is 1 SH2 domain present at the COOH-terminus of the molecule.
No evidence for alternative splicing has been obtained. Message stability has not been studied. While the human SLP-76 transcripts contain a relatively short 3' UTR, the murine transcript contains a relatively long 3' UTR with several potential AU-rich elements.
Tyrosine residues at positions 113 and 128 are the predominant sites of phosphorylation following TCR ligation. The tyrosine at position 145 may also be a candidate for phosphorylation. There is also evidence for constitutive serine phosphorylation in the acidic domain, although the exact serine residues involved have not been mapped.
| LIGANDS AND MOLECULES ASSOCIATED WITH SLP-76|
| SLP-76 functions to promote proliferation, differentiation and allelic exclusion in immature thymocytes following pre-TCR ligation and activation of mature T cells following ligation of the TCR. SLP-76 is required to couple the collagen receptor(s) expressed on platelets with more distal signaling events leading to aggregation and granule release. SLP-76 connects high affinity IgE receptor, Fce RI to downstream effectors responsible for degranulation and cytokine production in mast cells. A number of SLP-76 associated molecules have been identified, however it is not clear how SLP-76 and any associated proteins function to regulate the processes outlined above. Using SLP-76 deficient T cell lines or mice have provided strong evidence that SLP-76 plays a positive role in promoting T cell development and activation as well as mast cell and platelet function.|
SLP-76 has no enzymatic activity and appears to function primarily as an adaptor or scaffold protein.
DISEASE RELEVANCE AND FUNCTION OF SLP-76 IN INTACT ANIMAL
To date, no SLP-76 related human disease or pathology has been reported. Mice made deficient for SLP-76 by targeted disruption of the SLP-76 genomic locus manifest a complete block in thymocyte development at an early stage of maturation. SLP-76 deficient mice also exhibit a diffuse bleeding diathesis and selectively perish at or shortly after birth. SLP-76 deficient mice are resistant to IgE mediated anaphylaxis. SLP-76 deficient platelets fail to respond to collagen and fibrinogen while maintaining responsiveness to thrombin. The relationship between collagen dependent platelet dysfunction and bleeding has not been established.
| SLP-76 has been implicated in the regulation of actin polymerization and cytoskeletal changes associated with TCR ligation. Overexpression of SLP-76 in a T cell line potentiates Erk phosphorylation and activation as well as transcriptional activation of AP-1 and NF-AT. SLP-76 expression is required to promote tyrosine phosphorylation of PLCg1 in T cells and in mast cells and PLCg2 platelets.|
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF SLP-76: No information.
SLP-76 is not an enzyme, and therefore does not have any substrates in the enzymatic sense.
ENZYMES WHICH MODIFY SLP-76
SLP-76 is a member of the growing family of adaptor proteins that have been found to be critical signaling intermediates in many cell types. SLP-76 and adaptor proteins in general function to direct the assembly of macro-molecular signaling complexes which are in response to receptor ligation. Adaptor proteins are capable of effectively propagating signals that emanate from receptor and non-receptor tyrosine kinases and disseminating these signals into various biochemical pathways.
Database accession numbers
Revised June 25, 2008