MAP2K1 (Dual specificity mitogen-activated protein kinase kinase 1)

FEATURES

FAMILY

DESCRIPTION

Also known as MP2K1_HUMAN, MAP2K1, MEK1, PRKMK1. Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126). Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis. Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3/ERK1 and RGS14 (By similarity). Forms a heterodimer with MAP2K2/MEK2 (By similarity). Forms heterodimers with KSR2 which further dimerize to form tetramers (By similarity). Interacts with KSR1 or KSR2 and BRAF; the interaction with KSR1 or KSR2 mediates KSR1-BRAF or KSR2-BRAF dimerization (PubMed:10409742, PubMed:29433126). Interacts with ARBB2, LAMTOR3, MAPK1/ERK2 and RAF1 (By similarity). Interacts with MORG1 (By similarity). Interacts with PPARG (PubMed:17101779). Interacts with isoform 1 of VRK2 (PubMed:20679487). Interacts with SGK1 (PubMed:19447520). Interacts with BIRC6/bruce (PubMed:18329369). Interacts with KAT7; the interaction promotes KAT7 phosphorylation (By similarity). Interacts with RAF1 and NEK10; the interaction is required for ERK1/2-signaling pathway activation in response to UV irradiation (PubMed:20956560). Interacts with TRAF3IP3 (PubMed:26195727).

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EXTERNAL LINKS

MAP2K1

Dual specificity mitogen-activated protein kinase kinase 1

MOLECULAR SYNOPSIS STRUCTURAL LIGANDABILITY

MAP2K1

Molecular Synopsis