Disease relevance of EGFR

• Gel filtration further revealed that uterine flushings and fluids contained, respectively, 45 kDa and 40-70 kDa moieties that were mitogenic and that bound to the EGF receptor [1].
• BACKGROUND: We hypothesized that compensatory lung growth after lobectomy is characterized by a combination of cellular hyperplasia and hypertrophy and that up-regulation of epidermal growth factor receptor (EGFR) is involved in these processes [2].
• Immunohistochemical analysis of EGF-R in gastric mucosa in portal hypertensive with cirrhosis [3].
• Microscopically, the portal hypertension (PHT) group imparted "feeble positivity" or "negative results" and the control group showed "strong positivity". It was suggested that the decrease of EGF-R content in gastric mucosa weakened defense mechanism of gastric mucosa and increase its vulnerability [3].
• EGF in sera as well as in indifferently prepared IG of patients with recurrent goitre (n = 23), Graves' disease (n = 19) and normals (n = 17) was determined by EGF receptor assay [4].

High impact information on EGFR

• Substitution of these lysine residues with arginines resulted in a dramatic decrease in overall ubiquitination but preserved normal tyrosine phosphorylation of EGFR [5].
• To elucidate the role of EGFR ubiquitination, tandem mass spectrometry was used to identify six distinct lysine residues within the kinase domain of the EGFR, which can be conjugated to ubiquitin following growth factor stimulation [5].
• Taken together, these data provide direct evidence for the role of EGFR ubiquitination in receptor targeting to the lysosome and implicate Lys63-linked polyubiquitin chains in this sorting process [5].
• The amino acid sequence of porcine protein II reported here sheds new light on the properties of a multigene protein family which includes the tyrosine kinase substrates of the sarc gene (p36) and of the EGF-receptor (p35) [6].
• Moreover, transfection of a bacterial 14,15-epoxygenase established intracellular endogenous 14,15-EET biosynthesis in cultured cell systems, which allowed direct confirmation of involvement of EGFR transactivation in the endogenous 14,15-EET-mediated mitogenic signaling pathway [7].

Biological context of EGFR

• The aim of our study was to determine EGF and EGFR immunoexpression in the uterine artery and its branches during the estrous cycle in the pig [8].
• A significant decrease in the intensity of EGF and EGFR immunoreactivity was found in the middle luteal phase [8].
• The highest intensity of EGF and EGFR immunoreaction in endothelial cells of the uterine artery was observed in the follicular phase [8].
• Epidermal growth factor (EGF) and its receptor (EGFR) are expressed in many tissues, including reproductive organs, and is involved in angiogenesis, embryo implantation and development as well as in proliferation and differentiation of various cells [8].
• We conclude that the restricted presence of the functional full-size receptor to the epithelial layer indicates a specific role during early embryonic development, whereas truncated EGF-R forms may potentially regulate contractions and blood flow in the oviduct [9].

Anatomical context of EGFR

• Light microscopic observations revealed the phase-related immunoreactivity of EGF and EGFR in the endothelial cells of the uterine artery and its branches [8].
• The phase-related expression of EGF and EGFR in the endothelium of the uterine artery and its branches suggest the modulatory effect of EGF and its receptor on the uterine artery and the region supplying these vessels [8].
• Estrous cycle specific immunolocalization of different domains of the epidermal growth factor receptor in the porcine oviduct [9].
• In diestrous and proestrous stages, we found a low level of cytoplasmic but no extracellular EGF-R staining in epithelial cells [9].
• While the staining intensity of cytoplasmic domain of the EGF-R was only faint or absent in muscular tissue and blood vessels throughout the estrous cycle, extracellular domain of the EGF-R exhibited a strong immunostaining of smooth muscle cells and vascular smooth muscle cells, especially in diestrous and proestrous stages [9].

Associations of EGFR with chemical compounds

• Consistent with this notion, this action was blocked by the PTKs inhibitor genistein and the EGFR antagonist PD153035, indicating that contraction was, at least in part, attributable to PTKs phosphorylation that activates VR1, resulting in increased intracellular calcium content in the smooth muscle cells [10].
• In addition, 14, 15-EET-SI administration stimulated tyrosine phosphorylation of src homologous and collagen-like protein (SHC) and association of SHC with both growth factor receptor-binding protein (GRB2) and EGFR [11].
• Tyrosine phosphorylation of the EGFR by H(2)O(2) did not involve receptor autophosphorylation at Tyr(1173) as assessed by an autophosphorylation-specific antibody [12].
• Depletion of caveolin-1 also significantly reduced the ouabain-induced accumulation of Na/K-ATPase alpha-1 subunit, EGFR, Src, and MAPKs in clathrin-coat vesicles, as well as early and late endosomes [13].
• RESULTS: In wild-type LLC-PK1 cells, depletion of cholesterol by methyl beta-cyclodextrin reduced ouabain-induced accumulation of Na/K-ATPase alpha-1 subunit, EGFR, Src, and MAPKs in clathrin-coated vesicles, as well as in endosomes [13].

Enzymatic interactions of EGFR

• Focal adhesion kinase was tyrosine phosphorylated more by basolateral than by apical EGFR; however, beta-catenin was tyrosine phosphorylated to a much greater degree following the activation of mislocalized apical EGFR [14].
• The EGF receptor in Day 13 conceptus membranes is a 170-kDa protein and was phosphorylated in the presence of EGF and adenosine triphosphate [15].

Regulatory relationships of EGFR

• TGHQ, H(2)O(2), and EGF induce different EGFR tyrosine phosphorylation profiles that likely influence the subsequent differential kinetics of MAPK activation [16].

Other interactions of EGFR

• We isolated a PAC clone containing the porcine gene for LIFR and a BAC clone with the porcine EGFR gene, respectively [17].
• We conclude that a FSH-dependent pathway has an important role in the maturation of the EGFR in cumulus cells and that activation of EGFR-dependent signaling is sufficient to induce expansion [18].
• Expression of the genes for TGF alpha, EGF and the EGF receptor during early pig development [19].
• RESULTS: With the exception of vascular endothelial growth factor, immunoreactivity for all other growth factors studied and epidermal growth factor receptor was observed throughout normal non-lasered control retina, generally being high in the retinal pigment epithelium and low in the neural retina [20].
• The causative oncogene, Xmrk, encodes a receptor tyrosine kinase closely related to human epidermal growth factor receptor (EGFR) [21].

Analytical, diagnostic and therapeutic context of EGFR

• Moreover, immunoblotting indicated that 14,15-EET stimulated tyrosine phosphorylation of the specific pp60(c-src) substrate p120 and c-Src association with EGFR [11].
• Estrogen receptor a protein, and messenger ribonucleic acid (mRNA) and EGFR mRNA expression were analyzed in frozen tissue using Western blotting and semiquantitative reverse transcriptase polymerase chain reaction [22].
• The last group underwent a sham left thoracotomy, and the left lower lobe was harvested 2 weeks later for EGFR analysis [2].
• Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) documented lower expression of EGFR in the gastric juice group (P = .01) [23].
• Genomic DNAs of cattle, horses, pigs, dogs, cats and chickens were surveyed using Southern blot hybridization analysis, with a human EGFR cDNA fragment [24].

References