PMID: 9430688 RLIMS-P 11 Check other iTextMine results Issue Report
Title
1. | Identification of regulatory phosphorylation sites in mitogen-activated protein kinase (MAPK)-activated protein kinase-1a/p90rsk that are inducible by MAPK. |
Abstract
2. | Mitogen-activated protein kinase-activated protein kinase-1 (MAPKAP-K1; also known as p90rsk) contains two protein kinase domains in a single polypeptide. |
3. | The N-terminal kinase domain is necessary for the phosphorylation of peptide substrates, whereas the C-terminal kinase domain is required for full activation of the N-terminal domain. |
4. | Here we identify six sites in MAPKAP-K1a that become phosphorylated in transfected COS-1 cells. |
5. | The inactive form of MAPKAP-K1a in unstimulated cells is partially phosphorylated at Ser222 and Ser733. |
6. | Stimulation with phorbol 12-myristate 13-acetate induces the phosphorylation of Thr360, Ser364, Thr574, and Ser381 and increases the phosphorylation of Ser222 and Ser733. |
7. | Our data indicate that mitogen-activated protein kinase activates the C-terminal kinase domain by phosphorylating Thr574 and contributes to the activation of the N-terminal kinase domain by phosphorylating Ser364. |
8. | The activated C-terminal domain phosphorylates Ser381, which, together with phosphorylation of Ser364, activates the N-terminal kinase domain. |
9. | The phosphorylation of Ser222 and Ser733, which can be catalyzed by the N-terminal domain, does not activate MAPKAP-K1a per se, but Ser222 phosphorylation appears to be required for activation. |
10. | Ser222, Ser364, and Ser381 are situated in analogous positions to phosphorylation sites in protein kinase B, protein kinase C, and p70S6K, suggesting a common mechanism of activation for these growth factor-stimulated protein kinases. |
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Legend: SUBSTRATE KINASE INTERACTANT SITE GENE MIRNA ANOMALY EXPRESSION DISEASE OUTCOME/RESPONSE SR_DRUG DRUG CELL TRIGGER Normalized
Tool: RLIMS-P
PTM enzyme | Substrate | Site | Sentence |
---|---|---|---|
MAPKAP-K1a | Ser-222, Ser-733 | 5 | |
mitogen-activated protein kinase (MAPK)-activated protein kinase-1a/p90rsk | 1 | ||
MAPKAP-K1a | Ser-381 | 5, 8 | |
MAPKAP-K1a | Ser-364 | 5, 8 | |
MAPKAP-K1a | Ser-733, Ser-222 | 5, 6, 9 | |
MAPKAP-K1a | Thr-574, Ser-381, Thr-360, Ser-364 | 5, 6 | |
MAPKAP-K1a | Ser-222 | 5, 9 | |
protein kinase C | 10 | ||
protein kinase B | 10 | ||
MAPKAP-K1a | 4 | ||
p70S6K | 10 |