loading...| Preferred Name | Generation of second messenger molecules | |
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| Definitions |
Reviewed: Trowsdale, J, 2008-02-26 12:02:59 Authored: Rudd, C.E., de Bono, B, Garapati, P V, 2008-01-24 15:53:10 In addition to serving as a scaffold via auto-phosphorylation, ZAP-70 also phosphorylates a restricted set of substrates following TCR stimulation - including LAT and SLP-76. These substrates have been recognized to play pivotal role in TCR signaling by releasing second messengers. When phosphorylated, LAT and SLP-76 act as adaptor proteins which serve as nucleation points for the construction of a higher order signalosome: GADS, PLC-gamma1 and GRB2 bind to the LAT on the phosphorylated tyrosine residues (steps 8 and 13). SLP-76 and SOS are then moved to the signalosome by interacting with the SH3 domains of GRB2 and GADS via their proline rich sequences (step 9). Three SLP-76 acidic domain N-term tyrosine residues are phosphorylated by ZAP-70, once SLP-76 binds to GADS (step 10). These phospho-tyrosine residues act as binding sites to the SH2 domains of PLC-gamma1, Vav and Itk (steps 11 and 12). <p>PLC-gamma1 is activated by dual phosphorylation on the tyrosine residues at positions 771, 783 and 1254 by Itk and ZAP-70 (step 14). Phosphorylated PLC-gamma1 subsequently detaches from LAT and SLP-76 and translocates to the plasma membrane by binding to phosphatidylinositol-4,5-bisphosphate (PIP2) via its PH domain (step 15). PLC-gamma1 goes on to hydrolyse PIP2 to second messengers DAG and IP3. These second messengers are involved in PKC and NF-kB activation and calcium mobilization (step 16). |
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| ID |
http://purl.obolibrary.org/obo/HINO_0026238 |
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| comment |
Reviewed: Trowsdale, J, 2008-02-26 12:02:59 Authored: Rudd, C.E., de Bono, B, Garapati, P V, 2008-01-24 15:53:10 In addition to serving as a scaffold via auto-phosphorylation, ZAP-70 also phosphorylates a restricted set of substrates following TCR stimulation - including LAT and SLP-76. These substrates have been recognized to play pivotal role in TCR signaling by releasing second messengers. When phosphorylated, LAT and SLP-76 act as adaptor proteins which serve as nucleation points for the construction of a higher order signalosome: GADS, PLC-gamma1 and GRB2 bind to the LAT on the phosphorylated tyrosine residues (steps 8 and 13). SLP-76 and SOS are then moved to the signalosome by interacting with the SH3 domains of GRB2 and GADS via their proline rich sequences (step 9). Three SLP-76 acidic domain N-term tyrosine residues are phosphorylated by ZAP-70, once SLP-76 binds to GADS (step 10). These phospho-tyrosine residues act as binding sites to the SH2 domains of PLC-gamma1, Vav and Itk (steps 11 and 12). PLC-gamma1 is activated by dual phosphorylation on the tyrosine residues at positions 771, 783 and 1254 by Itk and ZAP-70 (step 14). Phosphorylated PLC-gamma1 subsequently detaches from LAT and SLP-76 and translocates to the plasma membrane by binding to phosphatidylinositol-4,5-bisphosphate (PIP2) via its PH domain (step 15). PLC-gamma1 goes on to hydrolyse PIP2 to second messengers DAG and IP3. These second messengers are involved in PKC and NF-kB activation and calcium mobilization (step 16). |
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| definition source |
Reactome, http://www.reactome.org Pubmed15084594 |
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| label |
Generation of second messenger molecules |
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| located_in | ||
| prefixIRI |
HINO:0026238 |
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| prefLabel |
Generation of second messenger molecules |
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| seeAlso |
ReactomeREACT_12623 Reactome Database ID Release 43202433 |
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| has_part |
http://purl.obolibrary.org/obo/HINO_0017842 http://purl.obolibrary.org/obo/HINO_0017841 http://purl.obolibrary.org/obo/HINO_0017840 http://purl.obolibrary.org/obo/HINO_0017849 http://purl.obolibrary.org/obo/HINO_0017843 http://purl.obolibrary.org/obo/HINO_0017829 http://purl.obolibrary.org/obo/HINO_0017828 http://purl.obolibrary.org/obo/HINO_0017827 http://purl.obolibrary.org/obo/HINO_0017834 http://purl.obolibrary.org/obo/HINO_0017836 http://purl.obolibrary.org/obo/HINO_0017835 http://purl.obolibrary.org/obo/HINO_0017838 http://purl.obolibrary.org/obo/HINO_0017833 http://purl.obolibrary.org/obo/HINO_0017837 http://purl.obolibrary.org/obo/HINO_0017839 |