Document Detail

Sprouty2 regulates growth and differentiation of human neuroblastoma cells through RET tyrosine kinase.
MedLine Citation:
PMID:  17388787     Owner:  NLM     Status:  MEDLINE    
The Sprouty (SPRY) family of proteins includes important regulators of downstream signaling initiated by receptor tyrosine kinases. In the present study, we investigated the role of SPRY proteins in intracellular signaling via the RET receptor tyrosine kinase activated by glial cell line-derived neurotrophic factor (GDNF). Expression of SPRY1, SPRY2, SPRY3 and SPRY4 in HEK293T cells transfected with RET and GDNF receptor family alpha1 (GFRalpha1) genes significantly reduced sustained ERK activation as well as ELK-1 activation. Because expression of SPRY2 was efficiently induced by GDNF in TGW human neuroblastoma cells expressing RET and GFRalpha1, we further investigated the role of SPRY2 in the growth and differentiation of TGW cells. Expression of wild-type SPRY2 (WT-SPRY2) decreased the growth of TGW cells. In contrast, expression of a dominant negative form of SPRY2 (MT-SPRY2, with a mutated tyrosine residue) enhanced cell proliferation. In addition, expression of WT-SPRY2 reduced GDNF-dependent neurite outgrowth of TGW cells, whereas expression of MT-SPRY2 enhanced it. Taken together, our results suggest that SPRY2 regulates GDNF-dependent proliferation and differentiation of TGW neuroblastoma cells mediated by RET tyrosine kinase.
Maki Ishida; Masatoshi Ichihara; Shinji Mii; Mayumi Jijiwa; Naoya Asai; Atsushi Enomoto; Takuya Kato; Ai Majima; Jiang Ping; Yoshiki Murakumo; Masahide Takahashi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-03-27
Journal Detail:
Title:  Cancer science     Volume:  98     ISSN:  1347-9032     ISO Abbreviation:  Cancer Sci.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-05-01     Completed Date:  2007-08-01     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  101168776     Medline TA:  Cancer Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  815-21     Citation Subset:  IM    
Department of Pathology, and Department of Mrfovs; Technology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
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MeSH Terms
Cell Differentiation
Cell Proliferation
Glial Cell Line-Derived Neurotrophic Factor / pharmacology
Intracellular Signaling Peptides and Proteins / physiology*
MAP Kinase Kinase Kinase 3 / metabolism
Neurites / drug effects
Neuroblastoma / enzymology*,  pathology*
Proto-Oncogene Proteins c-ret / metabolism*
Signal Transduction
Tumor Cells, Cultured
Reg. No./Substance:
0/Glial Cell Line-Derived Neurotrophic Factor; 0/Intracellular Signaling Peptides and Proteins; 0/SPRY2 protein, human; EC Proteins c-ret; EC Kinase Kinase Kinase 3

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