in turn phosphorylate the most downstream group of effector serine/threonine kinases, that
The JNK pathway is activated by environmental stress (oxidative stress) and cytokines (tumor necrosis factor, TNF, and FAS) and involves a kinase cascade similar to the ERK pathway with a MAPKKK activating a MAPKK and the MAPKK subsequently phosphorylating JNK on critical threonine and tyrosine residues resulting in the activation of JNK; afterwards JNK translocate to the nucleus and regulate the activity of multiple transcription factors.
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.
SHC-1 is an adaptor protein that connects MLK-1 and its downstream MAPKK
Incubation of RA SF with PD98059 or UO126, selective inhibitors of the MAPKK
Mek1 (proximal activator of Erk), dramatically inhibited MMP-1 secretion in response to IL-1[beta] or TNF-[alpha].
These stimuli activate MAPKK
kinases (MAPKKKs) via receptor dependent and independent mechanisms, followed by phosphorylation and activation of a downstream MAPK kinase (MAPKK
) and then MAPKs.
2], whereas in Arabidopsis, AtMPK3 and AtMPK6, the orthologs of WIPK and SIPK, were activated by MAPKK
kinase (MAPKKK), ANP1 (Kovtun et al.
On the basis of the observation that MAPKKK or NIK is required for the in vitro activation of IKK (33) and the identification of a canonical MAPKK
activation loop motif (SxxxS) on both IKK[alpha] and IKK[beta] (34-38), researchers have speculated that NIK is a direct upstream kinase that can phosphorylate and activate IKK[alpha] and IKK[beta].
The activation of MAPKKs
is regulated by other upstream serine-threonine kinases, called MAPKK
kinases, which phosphorylate the MAPKKs
on specific serine residues.
37 In addition, p38 MAPKs can be activated by MAPKKs
, MKK3 and MKK6.