Disease relevance of Ephb1

• Inhibition of hyposmotic Erk activation by pertussis or cholera toxin, erbstatin, or genistein had no effect on the swelling-induced inhibition of proteolysis [1].
• Regulation of Wallerian degeneration and nerve growth factor withdrawal-induced pruning of axons of sympathetic neurons by the proteasome and the MEK/Erk pathway [2].
• These data support a role for Ras and Erk signaling in MEM hyperplasia during bacterial OM [3].
• We examined localization of extracellular signal regulated kinases (Erk) 1 and 2, and c-fos mRNA expression in normal and ulcerated gastric mucosa in rats at 1, 3 and 7 days after gastric ulcer induction [4].

Psychiatry related information on Ephb1

• Administration of inhibitors of the Erk cascade worsened retrograde amnesia, impaired performances in hippocampus- and amygdala-dependent memory tasks, and exacerbated motor deficits following TBI [5].

High impact information on Ephb1

• SB 202190, a specific inhibitor of p38(MAPK), had no effect on TUDC- induced Erk activation but abolished the stimulatory effect of TUDC on TC excretion in perfused liver, indicating the requirement of p38(MAPK) in addition to the reported Erk dependence for the choleretic response [6].
• In the absence of depolarization, CaM-KKc transfection had no effect on Elk-dependent transcription of a luciferase reporter gene, whereas CaM-KIVc alone or in combination with CaM-KKc gave 7- to 10-fold and 60- to 80-fold stimulations, respectively, which were blocked by mitogen-activated protein (MAP) kinase phosphatase cotransfection [7].
• Integrin-mediated activation of EGFR in epithelial cells is required for multiple signal transduction events previously shown to be induced by cell adhesion to matrix proteins, including tyrosine phosphorylation of Shc, Cbl, and phospholipase Cgamma, and activation of the Ras/Erk and phosphatidylinositol 3'-kinase/Akt signaling pathways [8].
• It thus appears that the B-Raf/MEK/Erk pathway confers protection against apoptosis at the level of cytosolic caspase activation, downstream of the release of cytochrome c from mitochondria [9].
• We have recently established Rat-1 fibroblast cell lines overexpressing B-Raf, leading to activation of the MEK/Erk mitogen-activated protein kinase pathway [9].

Chemical compound and disease context of Ephb1

• Activation of Erk and of p70 S6 kinase via the D2 dopamine receptors was prevented by pretreatment of the cells with pertussis toxin, indicating the involvement of G proteins of the Gi or Go family [10].

Biological context of Ephb1

• In combination with others, our previous work has indicated that a K-Ras/Rac/JNK pathway is important for hair cell death and an H-Ras/Raf/MEK/Erk pathway is involved in promoting hair cell survival (Battaglia et al., Neuroscience 122(4):1025-1035, 2003) [11].
• In both amino acid sequence and overall structure, Elk is most similar to the Eph and Eck protein-tyrosine kinases, suggesting that the eph, elk, and eck genes encode members of a new subfamily of receptorlike tyrosine kinases [12].
• Expression of a dominant-negative Ras mutant resulted in a partial reversal of growth inhibition while expression of constitutively activated Ras led to Erk-dependent growth arrest, further demonstrating the role of the Ras/Erk pathway in this phenotype [13].
• Myocyte treatment with an activating antibody to erbB2 caused phosphorylation of erbB2, and led to activation of Erk but not Akt [14].
• B-Raf inhibits programmed cell death downstream of cytochrome c release from mitochondria by activating the MEK/Erk pathway [9].

Anatomical context of Ephb1

• Epidermal growth factor receptor induced Erk phosphorylation in the suprachiasmatic nucleus [15].
• These results also suggest a role of endogenous bFGF and CNTF in photoreceptor protection and the importance of Erk activation in photoreceptor survival [16].
• Thus, we propose that an additional step involving vesicle-mediated endocytosis is required for the rapid, Ras-dependent activation of Erk kinases in fibroblasts [17].
• Herein, we show that dPGJ2 activates, in cultured primary astrocytes, Erk, Jnk, p38 MAP kinase, and ASK1, a MAP kinase kinase kinase, which can be involved in the activation of Jnk and p38 MAP kinase [18].
• Role of the p66Shc isoform in insulin-like growth factor I receptor signaling through MEK/Erk and regulation of actin cytoskeleton in rat myoblasts [19].

Associations of Ephb1 with chemical compounds

• To investigate alternatives to the Ras/Raf/MEK/Erk pathway in promoting hair cell survival, cochlear explants were exposed to gentamicin combined with several inhibitors of alternative pathways (LY294002, calphostin C, SH-6, U73122) [11].
• The characteristics of the Elk tyrosine kinase suggest that it may be involved in cell-cell interactions in the nervous system [12].
• Glial-derived nerve factor (GDNF) induction by fluoxetine is prevented by U0126, suggesting that Erk is implicated [20].
• 5-Hydroxytryptamine (5-HT) activates the extracellular signal-regulated kinase (Erk) mitogen-activated protein kinases (MAPKs) in the vasculature, resulting in contraction [21].
• There are at least two distinct pathways by which glutamate signals through the SRE: an SRF-dependent pathway that can operate in the absence of Elk and an Elk-dependent pathway [22].

Other interactions of Ephb1

• The predicted Elk protein contains all the hallmarks of a receptor tyrosine kinase, including an N-terminal signal sequence, a cysteine-rich extracellular domain, a membrane-spanning segment, a cytoplasmic tyrosine kinase domain, and a C-terminal tail [12].

Analytical, diagnostic and therapeutic context of Ephb1

• Nuclear translocation of phospho-Erk was visualized by confocal microscopy [23].
• JNK inhibition also transiently blocked phosphorylation of c-Jun at 60 minutes after reperfusion (P<0.05) without affecting other MAPK signaling, including p-38 and Erk activation [24].
• Electrical stimulation for 24 h did not induce stress response (heat shock protein 70, 90) nor stress kinase (Erk, JNK, p38) activation [25].
• Human MAP kinases that are similar to the rat Erk kinases have also been identified by molecular cloning [26].

References