MAPK13 (p38 delta)

The p38 family of mitogen-activated protein kinases (MAPK) includes p38 alpha (SAPK2a, CSBP), p38 beta (SAPK2b), p38 delta (SAPK4), and p38 gamma (SAPK3/ERK6). p38 alpha and p38 beta are widely expressed p38 isoforms that are involved in regulation of cell proliferation, differentiation, development, and response to stress. p38 delta, also known as MAPK13, is a regulator of differentiation-dependent gene expression in keratinocytes, and been as a regulator of surface epithelia differentiation and apoptosis. p38 delta protein is upregulated in Cholangiocarcinoma (CC) relative to hepatocellularcarcinoma (HCC) and to normal biliary tract tissues. p38 delta is important for motility and invasion of CC cells, suggesting that p38 delta may play an important role in CC metastasis. p38 delta is expressed in the epidermis, suggesting a role for p38 delta in regulating differentiation. p38 delta is the major p38 isoform driving suprabasal involucrin gene expression and that p38 delta directly regulates ERK1/2 activity via formation of a p38 delta-ERK1/2 complex. Recent emerging evidence suggests that the p38 stress MAPK pathway may function as a tumor suppressor through regulating Ras-dependent and -independent proliferation, transformation, invasion and cell death by isoform-specific mechanisms. p38 delta has important role in promoting cell proliferation and tumor development in epidermis and may have therapeutic implication for skin cancer.

MAPK13 (p38 delta) Related Areas

Enzyme>>Protein Kinase>>Intracellular Kinase>>Mitogen-Activated Protein Kinase (MAPK)>>p38 delta/MAPK13

Signal Transduction>>Protein Kinase>>Intracellular Kinase>>Mitogen-Activated Protein Kinase (MAPK)>>p38 delta/MAPK13

MAPK13 (p38 delta) Alternative Names

p38 delta, MAPK13, RP1-179N16.4, MGC99536, PRKM13, SAPK4, p38delta [Homo sapiens]

p38 delta, Mapk13, RP24-313J18.2, SAPK4, Serk4 [Mus musculus]

Summaries for MAPK13 (p38 delta)

Entrez Gene summary for MAPK13 (p38 delta):

The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is closely related to p38 MAP kinase, both of which can be activated by proinflammatory cytokines and cellular stress. MAP kinase kinases 3, and 6 can phosphorylate and activate this kinase. Transcription factor ATF2, and microtubule dynamics regulator stathmin have been shown to be the substrates of this kinase.

OMIM - description for MAPK13 (p38 delta):

Mitogen-activated protein kinase (MAPK) cascades represent one of the major signal systems used by eukaryotic cells to transduce extracellular signals into cellular responses. The stress-activated protein kinases (SAPKs; see 601335) are MAPKs that are activated by chemical and environmental stresses as well as by proinflammatory cytokines. By screening a pituitary gland library with a partial SAPK2b (p38-beta; 602898) cDNA, Goedert et al. (1997) isolated cDNAs encoding a protein that they designated SAPK4. The sequence of the predicted 365-amino acid protein is approximately 60% identical to those of SAPK3 (p38-gamma; 602399), SAPK2a (p38; 600289), and SAPK2b. Like those SAPKs, SAPK4 has a TGY dual phosphorylation motif and is activated in response to cellular stresses and proinflammatory cytokines. MKK6 (601254) was found to be the major upstream activator of SAPK4. Goedert et al. (1997) reported that the substrate specificity of SAPK4 in vitro was similar to that of SAPK3. Northern blot analysis revealed that SAPK4 is expressed as a 2.3-kb transcript in a variety of tissues.

Wikipedia summary for MAPK13 (p38 delta):

Mitogen-activated protein kinase 13 (MAPK 13), also known as stress-activated protein kinase 4 (SAPK4), is an enzyme that in humans is encoded by the MAPK13 gene

Human MAPK13 (p38 delta) Protein General Information

 

• Protein names: Recommended name: Mitogen-activated protein kinase 13 Short name=MAP kinase 13 Short name=MAPK 13
• Sequence length: 365 AA.
• Domain: The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
• Sequence similarities: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. Contains 1 protein kinase domain.
• Post-translational modification: Dually phosphorylated on Thr-180 and Tyr-182 by MAP2K3/MKK3, MAP2K4/MKK4, MAP2K6/MKK6 and MAP2K7/MKK7, which activates the enzyme. Dephosphorylated by dual specificity phosphatase DUSP1.
• Catalytic activity: ATP + a protein = ADP + a phosphoprotein.
• Cofactor:

  Magnesium.

• Tissue specificity: Expressed in testes, pancreas, small intestine, lung and kidney. Abundant in macrophages, also present in neutrophils, CD4+ T-cells, and endothelial cells.

General information above from UniProt

Function for MAPK13 (p38 delta) Protein

UniProtKB:

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additionnal targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptionnal activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down-regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells

Genatlas:

• MAPK13 (p38 delta) has a protein serine/threonine kinase activity
• MAPK13 (p38 delta) phosphorylate transcription factor and downstreams targets

Homology for human MAPK13 (p38 delta)

• ortholog to murine Mapk13
• homolog to Drosophila p38b
• homolog to C.elegans pmk-1
• homolog to p38 alpha
• homolog to p38 beta
• homolog to p38 gamma