mitogen-activated protein kinase 14; mitogen-activated protein kinase p38 alpha; MAP kinase p38 alpha; cytokine suppressive anti-inflammatory drug-binding protein; CSAID-binding protein; CSBP; MAX-interacting protein 2; MAP kinase MXI2; SAPK2A (MAPK14, CSBP, CSBP1, CSBP2, CSPB1, MXI2)
Jump to navigation
Jump to search
Function
- responds to activation by environmental stress, pro-inflammatory cytokines & lipopolysaccharide (LPS) by phosphorylating a number of transcription factors, such as ELK1 & ATF2 & several downstream kinases, such as MAPKAPK2 & MAPKAPK5
- phosphorylates myelin basic protein, MAX, ATF2 & GADD153
- role in production of some cytokines, including IL-6
- may play a role in stabilization of EPO mRNA during hypoxic stress
- isoform Mxi2 activation is stimulated by mitogens & oxidative stress & only poorly phosphorylates ELK1 & ATF2
- isoform Exip may play a role in the early onset of apoptosis
- binds to a kinase interaction motif within the protein tyrosine phosphatase, PTPRR; this interaction retains MAPK14 in the cytoplasm & prevents nuclear accumulation
- interacts with SPAG9 (putative)
- interacts with NP60 & FAM48A
- activated by Thr & Tyr phosphorylation by either of two dual specificity kinases, MAP2K3 or MAP2K6, & potentially also MAP2K4
- can also be activated by autophosphorylation after interaction with TAB1 bypassing usual kinase cascade[2]. forms complex of TRAF6/TAB1/p38MAPK-alpha
- inhibited by dual specificity phosphatases, such as DUSP1
- inhibited by binding of pyridinyl-imidazole compounds, which are cytokine-suppressive anti-inflammatory drugs; isoform Mxi2 is 100-fold less sensitive to these agents than the other isoforms & is not inhibited by DUSP1
- isoform Exip is not activated by MAP2K6
- dually phosphorylated on Thr-180 & Tyr-182, which activates the enzyme
- phosphorylated upon DNA damage, probably by ATM or ATR
Structure
- TXY motif contains Thr & Tyrbwhose phosphorylation activates the MAP kinases
- belongs to the protein kinase superfamily, CMGC Ser/Thr protein kinase family, MAP kinase subfamily
- contains 1 protein kinase domain
Compartment
Alternative splicing
named isoforms=4; CSBP2, CSBP1, Mxi2, Exip
Expression
- brain, heart, placenta, pancreas & skeletal muscle
- expressed to a lesser extent in lung, liver & kidney
Pharmacology
- inhibitor of MAPK14 neflamapimod is an investigational agent for treatment of Alzheimer's disease
Notes
- some references seem to use p38 MAPK to refer to p38 MAPK-alpha as opposed to the p38MAPK subfamily of MAP kinases
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/Q16539.html
- ↑ 2.0 2.1 Ge B, Gram H, Di Padova F, Huang B, New L, Ulevitch RJ, Luo Y, Han J. MAPKK-independent activation of p38alpha mediated by TAB1- dependent autophosphorylation of p38alpha. Science. 2002 Feb 15;295(5558):1291-4. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11847341
- ↑ Wikipedia; Note: P38 mitogen-activated protein kinases entry http://en.wikipedia.org/wiki/P38_mitogen-activated_protein_kinases