2004
DOI: 10.1128/mcb.24.11.4636-4650.2004
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Mutations in the SAM Domain of the ETV6-NTRK3 Chimeric Tyrosine Kinase Block Polymerization and Transformation Activity

Abstract: The 12p13 ETV6 (TEL) gene is frequently targeted by chromosomal translocations in human malignancies, resulting in the formation of oncogenic ETV6 gene fusions. Many of the known partner genes encode protein tyrosine kinases (PTKs), generating fusion proteins that function as chimeric PTKs. ETV6-NTRK3 (EN), comprised of the ETV6 SAM domain fused to the NTRK3 PTK, is unique among ETV6 chimeric oncoproteins, as it is expressed in cancers of multiple lineages. We initially hypothesized that, similar to other ETV6… Show more

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Cited by 42 publications
(55 citation statements)
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“…5C) as previously shown for EN-transformed NIH 3T3 cells (63), while a punctate perinuclear and cytosolic pattern was observed in R Ϫ cells (Fig. 5B).…”
Section: Vol 26 2006 the Igf-i Receptor Suppresses Anoikis 1759supporting
confidence: 60%
See 1 more Smart Citation
“…5C) as previously shown for EN-transformed NIH 3T3 cells (63), while a punctate perinuclear and cytosolic pattern was observed in R Ϫ cells (Fig. 5B).…”
Section: Vol 26 2006 the Igf-i Receptor Suppresses Anoikis 1759supporting
confidence: 60%
“…EN contains the sterile alpha motif (SAM) oligomerization domain of the ETV6 (or TEL) transcription factor linked to the PTK domain of the neurotrophin 3 receptor NTRK3 (TRKC) (31). It is a predominantly cytosolic resident protein that undergoes ligand-independent PTK activation through SAM domain-mediated polymerization (63), leading to the constitutive induction of cyclin D1 and aberrant cell cycle progression (61). EN constitutively activates two of the major effector pathways of wild-type NTRK3, namely, the Ras-ERK and PI3K-Akt cascades, and both are required for EN transformation (61).…”
Section: Tidylinositol-3-kinase (Pi3k)-akt Activation and Undergo Detmentioning
confidence: 99%
“…Soft agar colony formation assays were done as described (23). Briefly, HEK293 cells were transiently transfected with each of the icRET constructs or a control plasmid (pTRE2).…”
Section: Methodsmentioning
confidence: 99%
“…The t (12;15) translocation in all of these tumors fuses sequences encoding the sterile a motif (SAM) domain of the ETS transcription factor, ETV6 (TEL), to the PTK domain of the neurotrophin-3 receptor, NTRK3 (TRKC). The SAM domain promotes EN polymerization and subsequent ligand-independent PTK activation (27). EN binds to and phosphorylates the insulin receptor substrates 1 and 2 (IRS1 and IRS2; ref.…”
Section: Introductionmentioning
confidence: 99%