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Rabbit Anti-phospho-ASK1 (Ser966)/FITC Conjugated antibody
background:
Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK). MAPKK kinase/MEKK phosphorylates and activates its downstream protein kinase, MAPK kinase/MEK, which in turn activates MAPK. The kinases of these signaling cascades are highly conserved, and homologs exist in yeast, Drosophila, and mammalian cells. MAPKKK5 contains 1,374 amino acids with all 11 kinase subdomains. Northern blot analysis shows that MAPKKK5 transcript is abundantly expressed in human heart and pancreas. The MAPKKK5 protein phosphorylates and activates MKK4 (aliases SERK1, MAPKK4) in vitro, and activates c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) during transient expression in COS and 293 cells; MAPKKK5 does not activate MAPK/ERK.
Function:
Component of a protein kinase signal transduction cascade. Phosphorylates and activates MAP2K4 and MAP2K6, which in turn activate the JNK and p38 MAP kinases, respectively. Overexpression induces apoptotic cell death.
Tissue Specificity:
Abundantly expressed in heart and pancreas.
Post-translational modifications:
Phosphorylated at Thr-838 through autophosphorylation and by MAP3K6/ASK2 which leads to activation. Thr-838 is dephosphorylated by PPP5C. Ser-83 and Ser-1033 are inactivating phosphorylation sites, the former of which is phosphorylated by AKT1 and AKT2. Phosphorylated at Ser-966 which induces association of MAP3K5/ASK1 with the 14-3-3 family proteins and suppresses MAP3K5/ASK1 activity. Calcineurin (CN) dephosphorylates this site. Also dephosphorylated and activated by PGAM5.
Ubiquitinated. Tumor necrosis factor (TNF) induces TNFR2-dependent ubiquitination leading to proteasomal degradation.
Similarity:
Belongs to the protein kinase superfamily.
STE Ser/Thr protein kinase family.
MAP kinase kinase kinase subfamily.
Database links:
Entrez Gene: 4217 Human
Entrez Gene: 21288 Mouse
Omim: 602448 Human
SwissProt: Q99683 Human
SwissProt: O35099 Mouse
Unigene: 186486 Human
Unigene: 6595 Mouse
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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