MAPK targets/ Nuclear events mediated by MAP kinases (Homo sapiens)
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Description
The major cytosolic target of activated ERKs are RSKs (90 kDa Ribosomal protein S6 Kinase). Active RSKs translocates to the nucleus and phosphorylates such factors as c-Fos(on Ser362), SRF (Serum Response Factor) at Ser103, and CREB (Cyclic AMP Response Element-Binding protein) at Ser133. In the nucleus activated ERKs phosphorylate many other targets such as MSKs (Mitogen- and Stress-activated protein kinases), MNK (MAP interacting kinase) and Elk1 (on Serine383 and Serine389). ERK can directly phosphorylate CREB and also AP-1 components c-Jun and c-Fos. Another important target of ERK is NF-KappaB. Recent studies reveals that nuclear pore proteins are direct substrates for ERK (Kosako H et al, 2009). Other ERK nuclear targets include c-Myc, HSF1 (Heat-Shock Factor-1), STAT1/3 (Signal Transducer and Activator of Transcription-1/3), and many more transcription factors.
Activated p38 MAPK is able to phosphorylate a variety of substrates, including transcription factors STAT1, p53, ATF2 (Activating transcription factor 2), MEF2 (Myocyte enhancer factor-2), protein kinases MSK1, MNK, MAPKAPK2/3, death/survival molecules (Bcl2, caspases), and cell cycle control factors (cyclin D1).
JNK, once activated, phosphorylates a range of nuclear substrates, including transcription factors Jun, ATF, Elk1, p53, STAT1/3 and many other factors. JNK has also been shown to directly phosphorylate many nuclear hormone receptors. For example, peroxisome proliferator-activated receptor 1 (PPAR-1) and retinoic acid receptors RXR and RAR are substrates for JNK. Other JNK targets are heterogeneous nuclear ribonucleoprotein K (hnRNP-K) and the Pol I-specific transcription factor TIF-IA, which regulates ribosome synthesis. Other adaptor and scaffold proteins have also been characterized as nonnuclear substrates of JNK.</div>
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DataNodes
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| Name | Type | Database reference | Comment |
|---|---|---|---|
| ADP | Metabolite | 16761 (ChEBI)  | |
| ATF-2 | Protein | P15336 (UniProt) | |
| ATF-2-P | Protein | P15336 (UniProt) | |
| ATP | Metabolite | 15422 (ChEBI) | |
| Activated MAPK
kinases ERK1/2, JNK, p38 | Unknown | REACT_21930 (Reactome) | |
| Activated Protein 1
(AP-1) heterodimer cJUN/ATF2 | Complex | REACT_21429 (Reactome) | |
| Activated Protein 1 (AP-1)
heterodimer cJUN/cFOS | Complex | REACT_21707 (Reactome) | |
| CREB | Protein | P16220 (UniProt) | |
| Cyclic-AMP-
dependent transcription factor ATF-1 | Protein | P18846 (UniProt) | |
| ELK1 | Protein | REACT_13391 (Reactome) | |
| ERK-specific DUSP | Unknown | REACT_12976 (Reactome) | |
| ERK1/2/5 | Protein | REACT_13316 (Reactome) | |
| H2O | Metabolite | 15377 (ChEBI) | |
| MEF2 | Protein | REACT_13049 (Reactome) | |
| MSK1 | Protein | O75582 (UniProt) | |
| Orthophosphate | Metabolite | 18367 (ChEBI) | |
| PP2A-ABdeltaC
complex | Complex | REACT_2369 (Reactome) | |
| Phospho-
ELK1 | Protein | REACT_13225 (Reactome) | |
| Phospho-
ERK1/2/5 | Protein | REACT_13301 (Reactome) | |
| Phospho-
Ribosomal protein S6 kinase | Protein | REACT_12696 (Reactome) | |
| Phospho-Cyclic-
AMP-dependent transcription factor ATF-1 | Protein | P18846 (UniProt) | |
| Phospho-ERK
dimer | Unknown | REACT_12827 (Reactome) | |
| Phospho-ERK5 | Protein | Q13164 (UniProt) | |
| Phospho-MAP
kinase-activated protein kinase 2 | Protein | P49137 (UniProt) | |
| Phospho-MAP kinase
p38 alpha/beta | Protein | REACT_12925 (Reactome) | |
| Phospho-MEF2 | Protein | REACT_12996 (Reactome) | |
| Phospho-MSK1 | Protein | O75582 (UniProt) | |
| Phosphorylated JNKs:
MAPK8, MAPK9, MAPK10 | Protein | REACT_22035 (Reactome) | |
| Ribosomal protein S6
kinase | Protein | REACT_13229 (Reactome) | |
| c-FOS | Protein | P01100 (UniProt) | |
| c-FOS -P | Protein | P01100 (UniProt) | |
| c-Jun | Protein | P05412 (UniProt) | |
| c-Jun-P | Protein | P05412 (UniProt) | |
| phospho-CREB | Protein | P16220 (UniProt) |
