MAPKAPK5
Description
The MAPKAPK5 (MAPK activated protein kinase 5) is a protein-coding gene located on chromosome 12.
MAP kinase-activated protein kinase 5 is an enzyme that in humans is encoded by the MAPKAPK5 gene. The protein encoded by this gene is a member of the serine/threonine kinase family. In response to cellular stress and proinflammatory cytokines, this kinase is activated through its phosphorylation by MAP kinases, including MAPK1/ERK, MAPK14/p38-alpha, and MAPK11/p38-beta. In vitro, this kinase phosphorylates heat shock protein HSP27 at its physiologically relevant sites. Two alternately-spliced transcript variants of this gene encoding distinct isoforms have been reported. A link between Alzheimer's disease and reduced levels of MAPKAPK5 has been proposed. Clinical trials may confirm if this is the case.
MAPKAPK5 is a tumor suppressor serine/threonine-protein kinase involved in mTORC1 signaling and post-transcriptional regulation. It phosphorylates FOXO3, ERK3/MAPK6, ERK4/MAPK4, HSP27/HSPB1, p53/TP53 and RHEB. It acts as a tumor suppressor by mediating Ras-induced senescence and phosphorylating p53/TP53. It is involved in post-transcriptional regulation of MYC by mediating phosphorylation of FOXO3: phosphorylation of FOXO3 leads to promote nuclear localization of FOXO3, enabling expression of miR-34b and miR-34c, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent MYC translation. It acts as a negative regulator of mTORC1 signaling by mediating phosphorylation and inhibition of RHEB. It is part of the atypical MAPK signaling via its interaction with ERK3/MAPK6 or ERK4/MAPK4: the precise role of the complex formed with ERK3/MAPK6 or ERK4/MAPK4 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPK (ERK3/MAPK6 or ERK4/MAPK4), ERK3/MAPK6 (or ERK4/MAPK4) is phosphorylated and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6 (or ERK4/MAPK4). It mediates phosphorylation of HSP27/HSPB1 in response to PKA/PRKACA stimulation, inducing F-actin rearrangement.
MAPKAPK5 is also known as MAPKAP-K5, MK-5, MK5, NCFD, PRAK.
