MAPKAPK5
MAPKAPK5 (MAP kinase-activated protein kinase 5, also known as PRAK or MK5) is a tumour suppressor serine/threonine kinase of the CAMK family. It acts downstream of MAP kinases and regulates mTORC1 signalling, senescence and post-transcriptional control. Browse Assay Genie's current range of MAPKAPK5 research reagents below, or read on for the biology behind the target.
MAPKAPK5 is a serine/threonine-protein kinase involved in mTORC1 signalling and post-transcriptional regulation. It phosphorylates FOXO3, ERK3/MAPK6, ERK4/MAPK4, HSP27/HSPB1, p53/TP53 and RHEB. As a tumour suppressor, it mediates Ras-induced senescence and phosphorylates p53. It also inhibits mTORC1 signalling by phosphorylating RHEB, and it phosphorylates HSP27 in response to PKA/PRKACA stimulation, which induces F-actin rearrangement.
MAPKAPK5 also contributes to post-transcriptional control of MYC. Phosphorylation of FOXO3 by the kinase promotes FOXO3 nuclear localisation, enabling expression of miR-34b and miR-34c. These two microRNAs bind the 3'UTR of the MYC transcript and prevent MYC translation. The kinase is further part of atypical MAPK signalling: on interaction with ERK3/MAPK6 or ERK4/MAPK4, the atypical MAPK is phosphorylated and in turn phosphorylates and activates MAPKAPK5, which then phosphorylates the ERK3 or ERK4 partner. The precise role of this complex remains unclear.
In response to cellular stress and proinflammatory cytokines, the kinase is activated by phosphorylation by MAP kinases including MAPK1/ERK, MAPK14/p38-alpha and MAPK11/p38-beta. It is found in the nucleus but translocates to the cytoplasm upon phosphorylation and activation. The MAPKAPK5 gene belongs to the MAPK activated protein kinase group and the CAMK Ser/Thr protein kinase family within the protein kinase superfamily. Two alternately spliced transcript variants encoding distinct isoforms have been reported. The mouse ortholog is Mapkapk5.
MAPKAPK5 mediates Ras-induced senescence and phosphorylates p53, making it a focus for studies of senescence and tumour suppression.
The kinase negatively regulates mTORC1 signalling by phosphorylating and inhibiting RHEB, linking it to growth-control pathways.
MAPKAPK5 forms complexes with ERK3/MAPK6 or ERK4/MAPK4 in a reciprocal phosphorylation cascade whose precise role is still being clarified.
Activated by p38 and ERK kinases under stress, MAPKAPK5 phosphorylates HSP27 and drives F-actin rearrangement after PKA stimulation.
MAPKAPK5 is a tumour suppressor serine/threonine kinase. It phosphorylates substrates including FOXO3, p53, RHEB, HSP27 and the atypical MAPKs ERK3 and ERK4. Through these it regulates mTORC1 signalling, Ras-induced senescence, MYC translation via miR-34b and miR-34c, and F-actin rearrangement.
MAPKAPK5 is also known as PRAK and MK5. Its earlier HGNC name was mitogen-activated protein kinase-activated protein kinase 5, and UniProt lists it as MAP kinase-activated protein kinase 5. Two alternately spliced transcript variants encoding distinct isoforms have been reported.
Yes. MAPKAPK5 belongs to the MAPK activated protein kinase (MAPKAPK) gene group and the CAMK Ser/Thr protein kinase family, alongside MAPKAPK2 and MAPKAPK3. The mouse ortholog is Mapkapk5; check the datasheet of any product for its validated reactivity.
Other MAPK-activated protein kinases from the same gene group, useful for comparing signalling downstream of MAP kinases.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q8IW41; product specifications from Assay Genie datasheets.