Disease relevance of MAPK1

• This effect was blocked by pretreatment with pertussis toxin, suggesting that G alpha(i) plays an important role in mediating EG-VEGF-induced activation of MAPK signaling [1].
• Our finding support the importance of specific PKC isozyme linked to MAPK pathway in the regulation of endothelial responses to hypoxia [2].
• It is concluded that alpha BC phosphorylation during ischemia is regulated by p38 MAPK but not by ERK 1/2 [3].
• Our previous studies have shown that 5-hydroxytryptamine (5-HT) induces cellular hyperplasia/hypertrophy through protein tyrosine phosphorylation, rapid formation of superoxide (O(2)(-)), and extracellular signal-regulated kinase (ERK)1/ERK2 mitogen-activated protein (MAP) kinase activation [4].
• Infection of BPASMCs with an adenovirus containing catalase inhibited both ERK1/ERK2 MAP kinase activation and DNA synthesis induced by 5-HT [4].

High impact information on MAPK1

• Pretreatment of SMC with thrombin for 4 hours markedly increased U 46619-induced mitogen-activated protein kinase activity, indicating thrombin-induced upregulation of functional thromboxane receptors in SMC [5].
• Pretreatment of BAEC with TPA attenuated the shear-induced mitogen-activated protein kinase phosphorylation, suggesting that shear stress and TPA share a similar signal transduction pathway in activating cells [6].
• This study shows that stimulation by thrombin very rapidly activates this chemokine at the transcriptional level, that 2 Elk1 binding elements located between -534 and -483 bp of the promoter are major thrombin response elements, that activation occurs via the Elk1 transcription factor, and that the latter is directly activated by MEK1/ERK2 [7].
• Fluid shearing (shear stress, 12 dynes/cm2 [1 dyne = 10(-5)N]) induced a transient and rapid activation of p21ras and preferentially activated c-Jun NH2 terminal kinases (JNK1 and JNK2) over extracellular signal-regulated kinases (ERK-1 and ERK-2) [8].
• TNP-470 had no effects on PDGF receptor autophosphorylation or early signal transduction, such as activation of mitogen-activated protein kinase and immediate early gene expression [9].

Chemical compound and disease context of MAPK1

• These data suggest that Ang II stimulates Src tyrosine kinase via a pertussis toxin-sensitive pathway, which in turn activates the MAPK pathway, resulting in increased eNOS protein expression in BPAECs [10].
• A major component of Ang II-induced MAPK activation was insensitive to pertussis toxin (PTX), although a minor PTX-sensitive component could not be excluded [11].

Biological context of MAPK1

• The p38 kinase inhibitor SB203580 (20 microM, 30 min) abolished Ser31 and Ser19 phosphorylation on TOH and partially inhibited ERK2 phosphorylation produced by AII [12].
• The data also indicate that the methyl Se-specific inhibitory effects on these proteins are rapid and primary actions, preceding or independent of inhibitory effects on mitogenic signaling at the level of MAPK1/2 and on cell growth and survival [13].
• Thus, this study demonstrates a novel role for the uPAR in endothelial cell signal transduction that involves the activation of FAK and MAPK, which are mediated by the receptor-binding domain of uPA [14].
• MEK1 inhibition resulted in lower levels of ERK2 activation and synthesis and higher levels of apoptosis [15].
• Incubation of EC with PD 98059, a specific mitogen-activated protein kinase kinase inhibitor, or transfection with Y185F, a dominant negative ERK2, strongly inhibited VEGF-activated JNK [16].

Anatomical context of MAPK1

• Transfection of endothelial cells with a CaMKII-specific inhibitory peptide (AA 281-309) reduced H(2)O(2) phosphorylation of p38 MAPK and ERK1/2 [17].
• The impaired membrane binding is associated with this mutant's inability to transduce several antitumorigenic signals as it fails to mediate phorbol ester-stimulated translocation of myristoylated alanine-rich protein kinase C substrate (MARCKS), to activate mitogen-activated protein kinase and to augment melatonin-stimulated neurite outgrowth [18].
• Histamine antagonizes serotonin and growth factor-induced mitogen-activated protein kinase activation in bovine tracheal smooth muscle cells [19].
• Potential role for ceramide in mitogen-activated protein kinase activation and proliferation of vascular smooth muscle cells induced by oxidized low density lipoprotein [20].
• SB 203580 inhibits p38 mitogen-activated protein kinase, nitric oxide production, and inducible nitric oxide synthase in bovine cartilage-derived chondrocytes [21].

Associations of MAPK1 with chemical compounds

• KN93 also prevented H(2)O(2) activation of p38 MAPK [17].
• Using two-dimensional immunoblotting we demonstrate that thrombin stimulation leads to increases in the tyrosine phosphorylation of 4 proteins, three different isoforms of P44 mitogen activated protein kinase (MAPK) and one isoform of P38 stress activated protein kinase (SAPK) [22].
• Glucose-induced ET-1 overexpression was inhibited by a general PKC inhibitor, GF109203X, and a mitogen-activated protein kinase kinase inhibitor, PD98059, but not by wortmannin, a phosphatidylinositol 3-kinase inhibitor [23].
• Ang II markedly inhibited DAX-1 protein expression in a time- and concentration-dependent manner (to 38.7 +/- 12.9% of controls at 3 nm after 6 h, p < 0.01), an effect that required de novo protein synthesis and ERK2/1 activation [24].
• Insulin-induced desensitization could be prevented if a specific inhibitor of phosphatidylinositol 3-kinase (LY294002), but not an inhibitor of mitogen-activated protein kinase (PD98059), was present during the preincubation period [25].

Enzymatic interactions of MAPK1

• In this study, we found that caveolin-1 is phosphorylated by p38 mitogen-activated protein kinase (MAPK) under a static condition [26].

Regulatory relationships of MAPK1

• Endogenous FGF1-induced activation and synthesis of extracellular signal-regulated kinase 2 reduce cell apoptosis in retinal-pigmented epithelial cells [15].
• Inhibition of tyrosine kinase, Src tyrosine kinase, protein kinase C, and mitogen-activated protein kinase activities all blocked VEGF-induced KDR up-regulation [27].
• The results show that MBPK-1 and MBPK-2 are protamine kinase-activating kinases and suggest that MBPK-1 and MBPK-2 may be related to mitogen-activated protein kinase [28].
• Protein kinase C mediates basic fibroblast growth factor-induced proliferation through mitogen-activated protein kinase in coronary smooth muscle cells [29].
• Akt-dependent phosphorylation of serine 1179 and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase 1/2 cooperatively mediate activation of the endothelial nitric-oxide synthase by hydrogen peroxide [30].

Other interactions of MAPK1

• In summary, redox-sensitive activation of p38 MAPK/HSP27 pathway or ERK1/2 in endothelial cells requires CaMKII [17].
• Both FGF1 and bcl-x synthesis are necessary for the reduction of apoptosis in retinal pigmented epithelial cells by FGF2: role of the extracellular signal-regulated kinase 2 [31].
• These experiments examined several aspects of FGF signaling and the contribution of endogenous FGF1 to activation of the extracellular signal-regulated kinase 2 (ERK2) [15].
• Therefore, MARCKS, a major in vivo substrate of protein kinase C, is also an in vivo substrate of proline-directed protein kinase(s) such as mitogen-activated protein kinase or Cdk5 kinase [32].
• Inhibition of phosphatidylinositol-3 kinase/Akt or mitogen-activated protein kinase signaling sensitizes endothelial cells to TNF-alpha cytotoxicity [33].

Analytical, diagnostic and therapeutic context of MAPK1

• The observed interaction between CLIC3 and ERK7 is the first demonstration of a stable complex between a protein that activates chloride ion transport and a member of the mitogen-activated protein kinase family of signal transducers [34].
• Anti-ERK and anti-phosphotyrosine western blots of the assay fractions verified an enhanced phosphorylation of ERK1 and ERK2 in PMA-treated fractions relative to control fractions [35].
• Two phosphoisoforms of PK40erk2 are formed in this process, which have a reduced gel mobility, very much like the ERK2 form obtained in cell culture by stimulation with growth factors [36].
• Protein sequence analysis suggests that PK40 is a form of the extracellular signal-regulated kinase ERK2 [36].
• Mitogen-activated protein kinase (MAP kinase) activator was purified 2000-fold from skeletal muscle, and proteins which co-purified with the activator were analysed after SDS/PAGE by renaturation and partial sequencing [37].

References