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 ETV6/TEL gene has been reported to fuse to PDGFRbetab MDS1/EVI1, BTL, ACS2, STL, JAK2, ABL, CDX2, TRKC, AML1, and MN1. Among them, PDGFRbeta, ABL, JAK2, and TRKC are tyrosine kinases (TK). We identified a novel ETV6 partner gene, ARG (ABL-related gene or ABL2), another TK gene in a cell line established from a patient with acute myelogenous leukemia (AML-M3) with a t(15;17)(q22;q11.2) and a t(1;12)(q25;p13), which has the remarkable feature to differentiate to mature eosinophils in culture with all-trans retinoic acid and cytokines. The ETV6/ARG transcripts consisted of exon 1 to 5 of ETV6 and the 3' portion of ARG starting from exon 1B or exon 2, resulting in an open reading frame for a fusion protein consisting of the entire PNT oligomerization domain of ETV6 and all of the functional domains of ARG including the TK domain. This is the same protein structure as identified in the other ETV6 TK fusion proteins. The reciprocal ARG/ETV6 transcript was not expressed, and the normal ETV6 allele was not deleted or rearranged. Although the ABL is known to be involved in various human malignancies, ARG has not been involved in human malignancies despite its high homology to ABL. Thus, this is the first report showing involvement of ARG in human leukemia. The ETV6/ARG protein may be involved in the unique differentiation capacity of this cell line. (Blood. 2000;95:2126-2131)
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PMID:A new ETV6/TEL partner gene, ARG (ABL-related gene or ABL2), identified in an AML-M3 cell line with a t(1;12)(q25;p13) translocation. 1070 84

We developed a method of clone proliferation promoting fusion genes whose proteins were activated by protein oligomerization through the helix-loop-helix region (PNT domain) of TEL. We inserted a cDNA library downstream of the PNT domain with a retrovirus vector. The resulting retrovirus infected cytokine-dependent 32D cells and cells with cytokine-independent growth were analyzed for the inserted cDNA. We cloned 25 independent fusion genes including seven kinds of partner genes. Six of the seven were a fusion of TEL with protein tyrosine kinase, LYN, HCK, FGR, SYK, FLT3, and TYK2. A serine/threonine kinase, ARAF1, was also found to fuse with TEL. These kinase fusion proteins included kinase domains with proper reading frames. These fusions may be a useful model for clarifying the downstream signal transduction of constitutive active kinase and this expression cloning method may provide a new tool with which to study cell proliferation signalling.
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PMID:Expression cloning of oligomerization-activated genes with cell-proliferating potency by pseudotype retrovirus vector. 1524 Jan 36