MAPK-ERK activity

Marin-Kuan, M., Nestler, S., Verguet, C., Bezengon, C., Piguet, D., Delatour, T., Mantle, P., Cavin, C. Schilter, B. (2007) MAPK-ERK activation in kidney of male tats chronically fed ochratoxin A at a dose causing a significant incidence of renal carcinoma. Toxicol. Appl. Pharmacol. 224,174-181. 

Valjent, E., Pages, C., Rogard, M., Besson, M.J., Maldonado, R., and Caboche, J., Delta 9-tetrahy-drocannabinol-induced MAPK/ERK and Elk-1 activation in vivo depends on dopaminergic transmission, Eur. J. Neurosci., 14, 342, 2001. 

CREB is also phosphorylated on serine 133 by stimulation of growth factor signaling cascades [63]. This occurs via a complex pathway involving MAPK cascades (Fig. 23-9). Thus, as outlined earlier, nerve growth factor and related neurotrophins that act on receptor tyrosine kinases lead to the successive activation of Ras, Raf, MEK and ERK. Activated ERK then phosphorylates and activates a serine-threonine kinase, RSK, particular subtypes of which directly activate CREB via the phosphorylation of serine 133. 

SKBR-3 Breast ERBB2 mainly formed homodimers and signaled via MAPK-ERK. Increased activated integrin (M andPAK2 3-D cultures more sensitive to trastuzmnab, correlating with clinical results. Enhanced interactions with ECM (106) 1 CD 3 3 3... 

Previous studies have reported that ERKs are characteristically associated with cell proliferation and protection from apoptosis (Bl, XI), while activation of JNK and p38 MAPK can promote apoptosis in many systems, including B lymphocytes (G5), cerebellar granule cells (K3), hematopoietic cells (K8), and neuronal cells (M3, XI). On the other hand, a recent report found that a pyridinyl imidazole, SB 202190, the specific inhibitor of p38 MAPK, by itself was sufficient to induce apoptosis in T lymphocyte Jurkat cells (N2). Moreover, Th-2-derived cytokine IL-5, the ERK activator and antiapoptotic factor for eosinophils, could also activate p38 MAPK in human eosinophils (BIO). We recently reported that cytokine IL-3, IL-5, and GM-CSF could prolong survival of human eosinophilic leukemic (EoL-1) cells through the transient activation of ERK (W15). On the other hand, activation of p38 MAPK in EoL-1 cells by the NSAID sodium salicylate (NaSal) could lead to apoptosis (W15). We also found that the suppression of ERK using ERK antisense phosphorothioate oligodeoxynucleotides could promote the apoptosis of peripheral blood eosinophils (W16). Moreover, we found that dexamethasone-induced apoptosis and activation of JNK and p38 MAPK activity in eosinophils are regulated by caspases (Z2). 

A further susceptible point for insulin-regulated signaling pathways is the ribosomal protein S6. Under the influence of insulin, S6 is phosphorylated by a specific protein kinase, the p70 kinase, resulting in increased levels of translation of certain mRNAs. Several pathways including the MAPK/ERK pathway (see chapter 10) and the Akt kinase pathway can contribute to the activation of the p70 kinase. 

The MAPK/ERK proteins are at the lower end of signal transduction within a MAPK module and are generally preceded by two other protein kinases (Fig. 10.2). The MAPK/ERK proteins receive the signal in the form of an activating phosphorylation by a preceding protein kinase known as MAP/ERK kinase (MEK) or also MAP kinase kinase (MAPKK). 

Fig. 10.2. Components and activation of the ERK pathway. Ordering and specificity of protein kinases in the ERK pathway. ExtraceUular signals are registered via receptor tyrosine kinases and passed on to the Ras protein. Ras GTP activates protein kinases belonging to the group of MAPKK kinases (Raf kinases and MEEKs). The MAPKK kinases phosphorylate the downstream group of protein kinases, the MAPKKs at two Ser residues. The MAPKKs phosphorylate the MAPKs (ERKl and ERK2) at a Tyr and a Thr residue, and thus are classified as dual specificity kinases. MAPK mitogenic activated protein kinase ERK extracellularly regulated kinase MEK MAP/ERK kinase MAPKK MAPK kinase MAPKKK MAPKK kinase MEKK MEK kinase.

M phase portion of mitotic cell cycle including mitosis and cytokinesis during which the cell separates the duplicated genome into two identical halves MAPK mitogen activated protein kinase MEK MAPK/ERK kinase MEKK MAPK/ERK kinase kinase... 

In addition to the P-Ser- and P-Thr-specific PPs described above, there are a number of P-Tyr-specific PPases that reverse the consequences of protein Tyr phosphorylation deriving from RTK and TK activation. Substrates include RTKs themselves and downstream Tyr-phosphorylated signalling proteins such as PKCy, MAPK (ERK), JAK/STAT receptors, kinases, STATs and the CDKs described above. 

Mitogen Activated Protein Kinases (MAPK) ERKs and JNKs... 

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