Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of the present study was to determine the frequency of amplifications of three different members of the erbB gene family in human glioblastoma multiforme (GBM). We investigated 47 glial tumors (37 GBM WHO grade IV, 5 anaplastic astrocytomas WHO III and 5 astrocytomas WHO II) by Southern and Western analysis, and immunocytochemistry. Gene amplification of erbB genes in human malignant gliomas was restricted to the EGF receptor (EGFR) gene, erbB-1. We found amplification of the EGFR gene in 49% (18/37) of GBM but not in the astrocytomas WHO II/III. The erbB-2 and erbB-3 genes showed no amplification in the tumor specimens investigated in this study. At the protein level we found overexpression of the EGF receptor in 86% (32/37) by Western analysis and in 92% (34/37) by immunocytochemistry. Expression of the ERBB2 protein was present in 54% (20/37) but immunoreactivity was much weaker than for EGF receptor and in most cases barely detectable by Western analysis and immunocytochemistry. The ERBB3 protein was not expressed in the glial tumors investigated in this study. Of the three erbB genes only gene amplification and overexpression of the EGF receptor seems to have an impact on tumor progression of human gliomas. Our data from immunohistochemistry indicate that ERBB2 expression in GBM is closely correlated with EGF receptor levels and is therefore not useful as an independent prognostic parameter.
 ...
PMID:Amplification and differential expression of members of the erbB-gene family in human glioblastoma. 776 96

Type 1 diabetes (T1D) is an autoimmune disease resulting from the complex interaction between multiple susceptibility genes, environmental factors and the immune system. Over 40 T1D susceptibility regions have been suggested by recent genome-wide association studies; however, the specific genes and their role in the disease remain elusive. The objective of this study is to identify the susceptibility gene(s) in the 12q13 region and investigate the functional link to the disease pathogenesis. A total of 19 SNPs in the 12q13 region were analyzed by the TaqMan assay for 1,434 T1D patients and 1,865 controls. Thirteen of the SNPs are associated with T1D (best p = 4x10(-11)), thus providing confirmatory evidence for at least one susceptibility gene in this region. To identify candidate genes, expression of six genes in the region was analyzed by real-time RT-PCR for PBMCs from 192 T1D patients and 192 controls. SNP genotypes in the 12q13 region are the main factors that determine ERBB3 mRNA levels in PBMCs. The protective genotypes for T1D are associated with higher ERBB3 mRNA level (p<10(-10)). Furthermore, ERBB3 protein is expressed on the surface of CD11c(+) cells (dendritic cells and monocytes) in peripheral blood after stimulation with LPS, polyI:C or CpG. Subjects with protective genotypes have significantly higher percentages of ERBB3(+) monocytes and dendritic cells (p = 1.1x10(-9)); and the percentages of ERBB3(+) cells positively correlate with the ability of APC to stimulate T cell proliferation (R(2) = 0.90, p<0.0001). Our results indicate that ERBB3 plays a critical role in determining APC function and potentially T1D pathogenesis.
 ...
PMID:Genetically dependent ERBB3 expression modulates antigen presenting cell function and type 1 diabetes risk. 2066 83

There are no effective therapies for the ~30% of human malignancies with mutant RAS oncogenes. Using a kinome-centered synthetic lethality screen, we find that suppression of the ERBB3 receptor tyrosine kinase sensitizes KRAS mutant lung and colon cancer cells to MEK inhibitors. We show that MEK inhibition results in MYC-dependent transcriptional upregulation of ERBB3, which is responsible for intrinsic drug resistance. Drugs targeting both EGFR and ERBB2, each capable of forming heterodimers with ERBB3, can reverse unresponsiveness to MEK inhibition by decreasing inhibitory phosphorylation of the proapoptotic proteins BAD and BIM. Moreover, ERBB3 protein level is a biomarker of response to combinatorial treatment. These data suggest a combination strategy for treating KRAS mutant colon and lung cancers and a way to identify the tumors that are most likely to benefit from such combinatorial treatment.
 ...
PMID:Intrinsic resistance to MEK inhibition in KRAS mutant lung and colon cancer through transcriptional induction of ERBB3. 2468 32