Search
mitogen-activated protein kinase 1, MAP-2 kinase, p42mapk, ERK2, ERT1, myelin basic protein [MBP] kinase E3 or RSK kinase 1
Function:
- role in both the initiation & regulation of meiosis, mitosis, & postmitotic functions in differentiated cells
- substrates for MAPK1 & MAPK3 include:
- amiloride-sensitive Na+ channel beta chain
- amiloride-sensitive Na+ channel gamma chain
- AML1 (PEBP2 alpha isoform B, runt related transcription factor 1)
- Amphiphysin 1
- BIM (Bcl2 like 11 isoform 1)
- BRF
- CD120a (TNF-R1 p55)
- Crystallin alpha B (heat shock protein beta 5)
- mCRY1 cryptochrome
- mCRY2 cryptochrome
- ETS1 transcription factor
- ETS translocation variant 1, ER81
- ELK1 transcription factor
- ELK3 (SAP-2 transcription factor)
- GAB1 (Grb2-associated binder 1)
- GAB2 (Grb2 associated binder 2)
- GATA-1 transcription factor
- Golgi reassembly stacking protein 1
- hnRNP-K heterogeneous nuclear ribonucleoprotein K
- hormone sensitive lipase
- heat shock transcription factor 1
- HIV1 alpha gag-MA protein
- hypoxia inducible factor 1 alpha
- Krueppel like factor 11 (TIEG-2)
- KSR1
- microtubule associated protein 2 (MAP2)
- MAP2K1
- myelin basic protein
- microtubule associated protein tau
- MNK1
- MNK2
- MSK1, MSK2
- Na+,K+ ATPase alpha(1)-subunit
- NFATc
- Paxillin
- PDE4D
- p90 ribosomal kinases, RSK1, RSK2, RSK3
- RNA Polymerase II
- p27KIP1 (CDK inhibitor 1B)
- SOS
- SP1
- SAP90 (synapse-associated protein 90, PSD-95)
- SREBP-2 sterol regulatory element binding protein 2
- TNF alpha converting enzyme, TACE, ADAM 17
- Tyrosine hydroxylase
- Vinexin beta, SH3 domain protein 4
- activated by phosphorylation on Tyr & Thr in response to insulin & NGF
- both phosphorylations are required for activity (putative)
- dually phosphorylated on Thr-185 & Tyr-187, which activates the enzyme
- Tyr phosphorylation occurs before Thr phosphorylation
- interacts with MORG1 (putative)
- binds to HIV-1 Nef through its SH3 domain; interaction inhibits its tyrosine-kinase activity
- interacts with HSF4
Cofactor: Mg+2 (putative)
Structure:
- TXY motif contains the Thr & Tyr whose phosphorylation activates the MAP kinases
- belongs to the protein kinase superfamily, CMGC Ser/Thr protein kinase family, MAP kinase subfamily
- contains 1 protein kinase domain
Expression:
- predominates in muscle & heart
- present in dentate granule cells & in pyramidal cells through hippocampus & adjacent temporal cortex [2].
Interactions
molecular events
General
extracellular signal regulated kinase [ERK] family protein
Properties
SIZE: entity length = 360 aa
MW = 41 kD
COMPARTMENT: cytoplasm
STATE: active state
MOTIF: alanine-rich region {2-9}
MOTIF: alanine residue (SEVERAL)
kinase domain
SITE: 25-313
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 31-39
ATP-binding site
NAME: ATP-binding site
SITE: 54-54
aspartate residue {D149}
TXY {185-187}
Thr phosphorylation site {T185}
Tyr phosphorylation site {Y187}
Thr phosphorylation site {T190}
References
- Pelech SL, Sanghera JS.
Mitogen-activated protein kinases: versatile transducers
for cell signaling.
Trends Biochem Sci. 1992 Jun;17(6):233-8. Review.
PMID: 1323888
- Pelech SL, Sanghera JS.
MAP kinases: charting the regulatory pathways.
Science. 1992 Sep 4;257(5075):1355-6. No abstract available.
PMID: 1382311
- Hyman et al Am J Pathol 144:565 1994
- http://www.kinasource.com
- Wikipedia; Note: extracellular signal-regulated kinase entry
http://en.wikipedia.org/wiki/extracellular_signal-regulated_kinase
Databases & Figures
OMIM 176948
UniProt P28482
Pfam PF00069
Entrez Gene 5594
Kegg hsa:5594
ENZYME 2.7.11.24
MAP kinase pathways