Product Name: ASK1 (839-845) pT842
Product Number: PE-04ARU01
Peptide Name: ASK1 (839-845) pT842
Product Use: This phosphopeptide may be useful as a substrate for screening the phosphatase activity of protein phosphatases. The peptide sequence is located in the protein kinase catalytic domain activation T-loop between subdomains VII and VIII. T842 phosphorylation is predicted to inhibit phosphotransferase activity.
Peptide Production Method: Solid-phase peptide synthesis
Peptide Origin: Homo sapiens
Peptide Sequence: FTG(pT)LQY
Peptide Modifications N Terminus: Free amino
Peptide Modifications C Terminus: Amide
Peptide Modifications Other: Phosphorylated
Storage Conditions: -20°C
Scientific Background: ASK1 (MAP3K5, MAPKKK5) is a protein-serine/threonine kinase that is a member of the STE group of protein kinases in the STE11 family. This kinase is moderate to highly expressed in most tested human tissues. ASK1 regulates apoptosis through mitochondria-dependent caspase activation. Overexpression of ASK1 induces apoptotic cell death. ASK1 interacts with members of the TRAF family and is activated by TRAF2 in the tumour necrosis factor-alpha (TNF) signalling pathway. ASK1 is activated by phosphorylation at T838 by MAP3K6 and inhibited by phosphorylation at S966 and S1033. It acts as an upstream activator of the MKK>JNK and MKK>p38 MAPK signal transduction cascades through the direct phosphorylation of different MAP kinases, such as MAP2K4 (MKK4), MAP2K3 (MKK3), MAP2K6 (MKK6), and MAP2K7 (MKK7). It is dephosphorylated and activated by PGAM5. ASK1 contains an N-terminal autoinhibitory domain. It is inhibited by phosphorylation at S966 and S1033, and by HIV-1 Nef. ASK1 appears to be a tumour suppressor protein (TSP) as the active form of the protein kinase normally acts to inhibit tumour cell proliferation. 24% of melanoma cell lines were found to contain mutations in the coding-regions of either MAP3K5 or the closely related kinase MAP3K9, often in the kinase catalytic domain.Loss of heterozygosity in MAP3K5 was observed in 85% of melanoma specimens, indicating that the previously observed mutations result in the loss-of-function in the protein. An I780F substitution, the most commonly observed mutant form of the kinase, inhibits phosphotransferase activity.