MEN2A-RET-induced cellular transformation by activation of STAT3

JJ Schuringa; K Wojtachnio; W Hagens; E Vellenga; CHCM Buys; R Hofstra; W Kruijer

MEN2A-RET-induced cellular transformation by activation of STAT3

JJ Schuringa, K Wojtachnio, W Hagens, E Vellenga, CHCM Buys, R Hofstra, W Kruijer^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

79 Citations (Scopus)

Abstract

The MEN2A oncogene encodes for a constitutive active member of the RET receptor tyrosine kinase family. Here, we report that MEN2A-RET activates Signal Transducer and Activator of Transcription 3 (STAT3) via two YxxV/Q STAT3 docking sites, Tyr752 and Tyr928. MEN2A-RET induces both Tyr705 and Ser727 phosphorylation of STAT3, and STAT3 serine phosphorylation is required for its maximal transcriptional activity. Stable NIH3T3 cell lines expressing both MEN2A-RET and STAT3 alpha but not STAT3 beta, are characterized by enhanced proliferation and cyclin-D1 promoter activity, and enhanced growth in soft agar. These data indicate that malignant cell growth induced by MEN2A-RET involves its activation of STAT3.

Original language	English
Pages (from-to)	5350-5358
Number of pages	9
Journal	Oncogene
Volume	20
Issue number	38
Publication status	Published - 30-Aug-2001

Keywords

Ret tyrosine kinase receptor
MEN2A
STAT3
cellular transformation
RECEPTOR TYROSINE KINASE
ENTERIC NERVOUS-SYSTEM
RET PROTOONCOGENE
SIGNAL-TRANSDUCTION
DOCKING SITE
V-SRC
MUTATIONS
GENE
PATHWAY
ASSOCIATION

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@article{3e0d21d0bb9348c59c916a92cb40530b,

title = "MEN2A-RET-induced cellular transformation by activation of STAT3",

abstract = "The MEN2A oncogene encodes for a constitutive active member of the RET receptor tyrosine kinase family. Here, we report that MEN2A-RET activates Signal Transducer and Activator of Transcription 3 (STAT3) via two YxxV/Q STAT3 docking sites, Tyr752 and Tyr928. MEN2A-RET induces both Tyr705 and Ser727 phosphorylation of STAT3, and STAT3 serine phosphorylation is required for its maximal transcriptional activity. Stable NIH3T3 cell lines expressing both MEN2A-RET and STAT3 alpha but not STAT3 beta, are characterized by enhanced proliferation and cyclin-D1 promoter activity, and enhanced growth in soft agar. These data indicate that malignant cell growth induced by MEN2A-RET involves its activation of STAT3.",

keywords = "Ret tyrosine kinase receptor, MEN2A, STAT3, cellular transformation, RECEPTOR TYROSINE KINASE, ENTERIC NERVOUS-SYSTEM, RET PROTOONCOGENE, SIGNAL-TRANSDUCTION, DOCKING SITE, V-SRC, MUTATIONS, GENE, PATHWAY, ASSOCIATION",

author = "JJ Schuringa and K Wojtachnio and W Hagens and E Vellenga and CHCM Buys and R Hofstra and W Kruijer",

year = "2001",

month = aug,

day = "30",

language = "English",

volume = "20",

pages = "5350--5358",

journal = "Oncogene",

issn = "0950-9232",

publisher = "Nature Publishing Group",

number = "38",

}

TY - JOUR

T1 - MEN2A-RET-induced cellular transformation by activation of STAT3

AU - Schuringa, JJ

AU - Wojtachnio, K

AU - Hagens, W

AU - Vellenga, E

AU - Buys, CHCM

AU - Hofstra, R

AU - Kruijer, W

PY - 2001/8/30

Y1 - 2001/8/30

N2 - The MEN2A oncogene encodes for a constitutive active member of the RET receptor tyrosine kinase family. Here, we report that MEN2A-RET activates Signal Transducer and Activator of Transcription 3 (STAT3) via two YxxV/Q STAT3 docking sites, Tyr752 and Tyr928. MEN2A-RET induces both Tyr705 and Ser727 phosphorylation of STAT3, and STAT3 serine phosphorylation is required for its maximal transcriptional activity. Stable NIH3T3 cell lines expressing both MEN2A-RET and STAT3 alpha but not STAT3 beta, are characterized by enhanced proliferation and cyclin-D1 promoter activity, and enhanced growth in soft agar. These data indicate that malignant cell growth induced by MEN2A-RET involves its activation of STAT3.

AB - The MEN2A oncogene encodes for a constitutive active member of the RET receptor tyrosine kinase family. Here, we report that MEN2A-RET activates Signal Transducer and Activator of Transcription 3 (STAT3) via two YxxV/Q STAT3 docking sites, Tyr752 and Tyr928. MEN2A-RET induces both Tyr705 and Ser727 phosphorylation of STAT3, and STAT3 serine phosphorylation is required for its maximal transcriptional activity. Stable NIH3T3 cell lines expressing both MEN2A-RET and STAT3 alpha but not STAT3 beta, are characterized by enhanced proliferation and cyclin-D1 promoter activity, and enhanced growth in soft agar. These data indicate that malignant cell growth induced by MEN2A-RET involves its activation of STAT3.

KW - Ret tyrosine kinase receptor

KW - MEN2A

KW - STAT3

KW - cellular transformation

KW - RECEPTOR TYROSINE KINASE

KW - ENTERIC NERVOUS-SYSTEM

KW - RET PROTOONCOGENE

KW - SIGNAL-TRANSDUCTION

KW - DOCKING SITE

KW - V-SRC

KW - MUTATIONS

KW - GENE

KW - PATHWAY

KW - ASSOCIATION

M3 - Article

SN - 0950-9232

VL - 20

SP - 5350

EP - 5358

JO - Oncogene

JF - Oncogene

IS - 38

ER -

MEN2A-RET-induced cellular transformation by activation of STAT3

Abstract

Keywords

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