Open AccessSprouty2 regulates growth and differentiation of human neuroblastoma cells through RET tyrosine kinase
Author(s) -
Ishida Maki,
Ichihara Masatoshi,
Mii Shinji,
Jijiwa Mayumi,
Asai Naoya,
Enomoto Atsushi,
Kato Takuya,
Majima Ai,
Ping Jiang,
Murakumo Yoshiki,
Takahashi Masahide
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00457.x
Subject(s) - glial cell line derived neurotrophic factor , gdnf family of ligands , receptor tyrosine kinase , microbiology and biotechnology , ror1 , cancer research , tyrosine kinase , biology , neurotrophic factors , signal transduction , platelet derived growth factor receptor , chemistry , receptor , growth factor , biochemistry
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 α1 (GFRα1) 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 GFRα1, 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. ( Cancer Sci 2007; 98: 815–821)