MAPK, mitogen-activated protein kinase; ERK, extracellular signal-related kinases; JNK, c-Jun N-terminal kinases; p38, p38 kinase; BMK1/ERK5, big MAP kinase 1; MAPKKK
, MAP kinase kinase kinase; MAPKK, MAP kinase kinase; MAPK, MAP kinase; PLC, phospholipase C; IP3, inositol trisphosphate; DAG, diacylglycerol.
An RNAi screen for regulators of axon regeneration identified the MAPKKK DLK-1.
An RNAi screen for regulators of axon regeneration also identified another MAPKKK, MLK-1, which is involved in the JNK pathway.
Western blotting analysis using COS-7 cells expressing MLK-1 MAPKKK and SVH-2 showed that MLK-1 and SVH-2 can physically interact.
The most likely target of TPA-1 in the context of axon regeneration is MLK-1 MAPKKK.
Results from these studies on SVH-1, SVH-2 and SVH-3/FAAH-1 indicate that the activity of MLK-1 MAPKKK in promoting axon regeneration is regulated by at least two independent mechanisms: it is serine phosphorylated by TPA, which induces its kinase activity, and it is tyrosine phosphorylated by SVH-2, which promotes its interaction with the downstream target MEK-1 MAPKK via the adaptor protein SHC-1 (Fig.
1995) Identification of a member of the MAPKKK family as a potential mediator of TGF-O signal transduction.
1996) TAB1: an activator of the TAK1 MAPKKK in TGF-[beta] signal transduction.
1997) Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways.
2000) TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway.
Activation of oxidative stress responses upon expression of a constitutively active derivative of the MAPKKK, ANP1, caused a simultaneous inhibition of the auxin response pathway (Yang et al.
Another study showed that a mutation in a putative Arabidopsis MAPKKK resulted in a mutant (edr1, improved disease resistance) with increased resistance to powdery mildew and Pseudomonas syringae without any phenotypic changes (Frye et al.