Serine/threonine kinase which acts as an essential componentof the MAP kinase signal transduction pathway. MAPK1/ERK2 andMAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERKcascade. They participate also in a signaling cascade initiated byactivated KIT and KITLG/SCF. Depending on the cellular context, theMAPK/ERK cascade mediates diverse biological functions such as cellgrowth, adhesion, survival and differentiation through the regulationof transcription, translation, cytoskeletal rearrangements. TheMAPK/ERK cascade plays also a role in initiation and regulation ofmeiosis, mitosis, and postmitotic functions in differentiated cells byphosphorylating a number of transcription factors. About 160 substrateshave already been discovered for ERKs. Many of these substrates arelocalized in the nucleus, and seem to participate in the regulation oftranscription upon stimulation. However, other substrates are found inthe cytosol as well as in other cellular organelles, and those areresponsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation ofthe endosomal dynamics, including lysosome processing and endosomecycling through the perinuclear recycling compartment (PNRC); as wellas in the fragmentation of the Golgi apparatus during mitosis. Thesubstrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (suchas BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators oftranslation (such as EIF4EBP1) and a variety of other signaling-relatedmolecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such asRAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 orMAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) areother substrates which enable the propagation the MAPK/ERK signal toadditional cytosolic and nuclear targets, thereby extending thespecificity of the cascade. Mediates phosphorylation of TPR in responseto EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading toPML degradation. Phosphorylates CDK2AP2.

MAAAAAAGAGPEMVRGQVFDVGPRYTNLSYIGEGAYGMVCSAYDNVNKVRVAIKKISPFEHQTYCQRTLREIKILLRFRHENIIGINDIIRAPTIEQMKDVYIVQDLMETDLYKLLKTQHLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTTCDLKICDFGLARVADPDHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHILGILGSPSQEDLNCIINLKARNYLLSLPHKNKVPWNRLFPNADSKALDLLDKMLTFNPHKRIEVEQALAHPYLEQYYDPSDEPIAEAPFKFDMELDDLPKEKLKELIFEETARFQPGYRS