Mitogen-activated protein (MAP) kinase, ERK1/2 (IPR008349)
Short name: MAPK_ERK1/2
Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity [PMID: 3291115]:
- Serine/threonine-protein kinases
- Tyrosine-protein kinases
- Dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)
Protein kinase function is evolutionarily conserved from Escherichia coli to human [PMID: 12471243]. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation [PMID: 12368087]. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [PMID: 15078142], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [PMID: 15320712].
MAP (Mitogen Activated Protein) kinases participate in kinase cascades, whereby at least 3 protein kinases act in series, culminating in activation of MAP kinase [PMID: 8607979, PMID: 10487205]. MAP kinases are activated by dual phosphorylation on both tyrosine and threonine residues of a conserved TXY motif.
ERKs (Extracellularly Regulated Kinases) belong to the family of MAP kinases. ERK1 (also known as MAPK3) and ERK2 (also known as MAPK1) are proteins of 43 and 41kDa respectively. They are ~85% identical, even higher levels of similarity being seen in substrate binding regions. Both are ubiquitously expressed, although levels vary from tissue to tissue. They are activated, for example, by serum, growth factors and cytokines. They phosphorylate both cytoskeletal proteins and transcription factors, resulting ultimately in cell growth. Substrates carry a PX(T/S)P motif; other such "docking domains" also exist within ERK, which interact with specific motifs in the substrate: e.g., ERK1 and ERK2 possess 2 DXXD docking sites capable of interaction with a Kinase Interaction Motif (KIM), which can be found on activators (MAPKK), inhibitors (PTP-SL and dual specificity phosphatases) and substrates (Elk-1).
- PR01770 (ERK1ERK2MAPK)