Disease relevance of MAPK1

• These data suggest that PEDF provides a useful support for retinal cells through the MAPK pathway and leads to the progress of therapy for many retinal diseases [1].
• Noonan syndrome and related disorders: dysregulated RAS-mitogen activated protein kinase signal transduction [2].
• Infectious bursal disease virus infection induces macrophage activation via p38 MAPK and NF-kappaB pathways [3].

Psychiatry related information on MAPK1

• Other agents known to inhibit these enzymes, including the Map kinase inhibitor Rapamycin, also induced memory deficits in a complex, dose- and time-of-administration-dependent, manner [4].

High impact information on MAPK1

• Involvement of guanosine triphosphatases and phospholipase C-gamma2 in extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38 mitogen-activated protein kinase activation by the B cell antigen receptor [5].
• Control of the segmentation process by graded MAPK/ERK activation in the chick embryo [6].
• Phosphorylation was increased on two mitogen-activated protein kinase (MAPK) sites, threonine 1179 and serine 1185 [7].
• This is due to the dismantling of Fgf signalling at distinct points of the MAPK signalling cascade in the neck lateral mesoderm and ectoderm [8].
• Here, we demonstrate that myotomally derived FGFs act through the MAPK signal transduction cascade and in particular, ERK1/2 to activate scleraxis expression in a population of mesenchymal progenitor cells in the dorsal sclerotome [9].

Biological context of MAPK1

• The pro-angiogenesis effect of the thyroid hormone analogs was blocked by PD 98059, an inhibitor of the mitogen-activated protein kinase (MAPK; ERK1/2) signal transduction cascade [10].
• Stimulation of heterophils with each specific TLR agonist led to a differential increase in the phosphorylation of both p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1/2 (ERK 1/2) activation, but not the phosphorylation of c-Jun NH2-terminal kinase (JNK) [11].
• Gene-disruption or -silencing often lead to lethal effects, therefore the zebrafish ex utero development provides an excellent in vivo model to study the function of MAPK in early embryogenesis [12].
• However, the pathways leading to the activation of downstream serine/threonine kinases such as mitogen-activated protein kinase, p90(Rsk), and p70S6 kinase (p70(S6k)) that mediate reorganization of the actin cytoskeleton, cell cycle progression, gene transcription, and protein synthesis have not been delineated [13].
• In the present study, we show that HMGB1 exerts proangiogenic effects by inducing MAPK ERK1/2 activation, cell proliferation, and chemotaxis in endothelial cells of different origin [14].

Anatomical context of MAPK1

• Indeed, EGF increased the translocation of PKC from the cytosol to the membrane fraction, and increased the activation of p44/42 MAPK, p38 MAPK, and JNK [15].
• PEDF possibly promotes neurite outgrowth for retinal cells by activating MAPK pathways [1].
• CONCLUSIONS: T(4), T(3), and T(4)-agarose are pro-angiogenic in the three-dimensional human microvascular endothelial sprouting model, an action that is initiated at the plasma membrane, involves avb3 integrin receptors, and is MAPK-dependent [10].
• Incubation of COS-1 cells with 8-bromo-cAMP resulted in activation of the MAPK pathway, as determined by Western blotting with antibodies to the phosphorylated (active) form of Erk-1/2, suggesting an indirect pathway to SRC-1 phosphorylation [7].
• The stem zone is a site of FGF/MAPK signalling and we show that although FGF alone does not mimic paraxial mesoderm signals, it is directly required in epiblast cells for stem zone specification and maintenance [16].

Associations of MAPK1 with chemical compounds

• In addition, PD 98059 (a MEK inhibitor), SB 203580 (a p38 MAPK inhibitor), and SP 600125 (a JNK inhibitor) blocked the EGF-induced stimulation of [(3)H]-thymidine incorporation and CDK-2/4 expression [15].
• The phosphodiesterase 5 inhibitor sildenafil stimulates angiogenesis through a protein kinase G/MAPK pathway [17].
• PDGF-BB also induced tyrosine phosphorylation and nuclear translocation of MAPK [18].
• The c-fos induction, the increased AP-1 binding activity and the acceleration of DNA synthesis were all attenuated by genistein (100 microM) or MAPK kinase inhibitor (10 or 50 microM PD98059) [18].
• We found that this stimulatory effect on the S phase is reverted by specific inhibitors of protein kinase C (PKC) and p42/44 mitogen-activated protein kinase (p42/44 MAPK), Ro 31-8220 or PD 98059 [19].

Enzymatic interactions of MAPK1

• Phosphopeptide mapping of caldesmon immunoprecipitated from [32P]PO4-labelled intact gizzard strips revealed that it is predominantly phosphorylated at mitogen-activated protein kinase sites in unstimulated tissue and that it is stimulated for 1 h with phorbol 12,13-dibutyrate [20].

Regulatory relationships of MAPK1

• p38 mitogen-activated protein kinase regulates oscillation of chick pineal circadian clock [21].
• Overexpression of Wnt-5a or treatment with TGF-beta3 stimulated the activation of protein kinase C-alpha (PKC-alpha) and p38 mitogen-activated protein kinase (MAPK), both positive regulators of chondrogenic differentiation [22].

Other interactions of MAPK1

• Using techniques to overexpress or suppress kinase activity, we find that calcium/calmodulin-dependent protein kinase II (CaMKII) and mitogen-activated protein kinase (MAPK) are major downstream targets of the netrin-1 calcium signaling pathway and are required for axon branching [23].
• We now report that intracellular signaling resulting in the activation of Map kinase (MapK) or translocation of Smad1 mediate the differentiation of CA neurons in response to CEE or BMP 4, respectively [24].
• The effect of direct phosphorylation by recombinant p44erk1 mitogen-activated protein kinase on the inhibitory activity of caldesmon and its C-terminal fragment H1 was studied in vitro [20].
• Treatment with TGFalpha or BTC increases levels of TGFbeta1 mRNA in undifferentiated granulosa cells, while the selective inhibitor of mitogen activated protein kinase signaling, U0126, reverses these effects [25].

Analytical, diagnostic and therapeutic context of MAPK1

• Gene-targeting approaches in mice, chickens, frogs and zebrafish revealed crucial roles of MAPK in vertebrate development [12].
• The phosphorylation of both MAPK ERK1/2 and p38 was also significantly higher after treatment with LHRH-I than LHRH-II, salmon LHRH or hyp9 [26].

References