MLK3 or Mixed-Lineage Kinase 3 is a mitogen-activated protein kinase kinase kinase capable of preferentially activating MAPK8/JNK kinase and functions as a positive regulator of JNK signaling pathway. MLK3 can directly phosphorylate and activate IkappaB kinase alpha and beta, and is found to be involved in the transcription activity of NF-kappaB mediated by Rho family GTPases and CDC42. MLK3 is a signal-integrating kinase with conventional MAP3K catalytic activity and additional noncatalytic functions that contribute to RAF/ERK signalling. MLK3 is a component of the BRAF/RAF1 complex and is required for integrity of the complex and for activation of ERK by the complex.
The ERK group of mitogen-activated protein kinases (MAPKs) is essential for cell proliferation stimulated by mitogens, oncogenic ras and raf (ref. 1). All MAPKs are activated by MAP3K/MEK/MAPK core pathways and the Raf proto-oncoproteins, especially B-Raf, are ERK-specific MAP3Ks (refs
We have identified a novel protein kinase, designated MLK-3, from human thymus using RT-PCR and cDNA library screening. The deduced open reading frame, derived from sequencing a 3.5 kb MLK-3 cDNA, encodes a protein of 847 amino acids with several
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