Reactome | ROS oxidize thioredoxin and activate MAP3K5

ROS oxidize thioredoxin and activate MAP3K5

Stable Identifier

R-HSA-3225851

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

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ROS oxidize thioredoxin and activate MAP3K5

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When in reduced form, TXN (thioredoxin) binds the amino terminus of MAP3K5 (ASK1) and inhibits its kinase activity. Once reactive oxygen species (ROS) oxidize TXN, TXN dissociates from MAP3K5, enabling MAP3K5 to phosphorylate downstream targets (Saitoh et al. 1998). Increased expression and activity of MINK1 (MINK) (and possibly other Ste20 family kinases TNIK and MAP4K), which is induced by ROS generated as a consequence of oncogenic RAS signaling, may contribute to MAP3K5 activation (Nicke et al. 2005).

Literature References

PubMed ID	Title	Journal	Year
16337592	Involvement of MINK, a Ste20 family kinase, in Ras oncogene-induced growth arrest in human ovarian surface epithelial cells Nicke, B, Bastien, J, Khanna, SJ, Warne, PH, Cowling, V, Cook, SJ, Peters, G, Delpuech, O, Schulze, A, Berns, K, Mullenders, J, Beijersbergen, RL, Bernards, R, Ganesan, TS, Downward, J, Hancock, DC	Mol. Cell	2005
9564042	Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1 Saitoh, M, Nishitoh, H, Fujii, M, Takeda, K, Tobiume, K, Sawada, Y, Kawabata, M, Miyazono, K, Ichijo, H	EMBO J.	1998