TY - JOUR
T1 - Calcium-dependent Ret activation by GDNF and neurturin
AU - Nozaki, Chika
AU - Asai, Naoya
AU - Murakami, Hideki
AU - Iwashita, Toshihide
AU - Iwata, Yosuke
AU - Horibe, Keizo
AU - Klein, Robert D.
AU - Rosenthal, Arnon
AU - Takahashi, Masahide
N1 - Funding Information:
We thank J Aoki and K Imaizumi for technical assistance; and K Watanabe for encouragement to this work. This work was supported by grants-in-aid for scientific research and for cancer research from the Ministry of Education, Science, Sports and Culture of Japan and by a grant from the Cell Science Research Foundation to MT.
PY - 1998/1/22
Y1 - 1998/1/22
N2 - Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) define a new family of neurotrophic factors that play crucial roles in survival and differentiation of various neurons. Recent studies demonstrated that GDNF and NTN use a multicomponent receptor system in which glycosol-phosphatidylinositol (GPI)-linked cell surface proteins and Ret receptor tyrosine kinase function as the ligand-binding and signalling components, respectively. In the present study, we investigated the role of Ca2+ ions for biochemical and biological activities of Ret because Ret has a unique structure of the extracellular domain with the cadherin-like motif. The results demonstrated that Ca2+ ions might be required for the complex formation of Ret and GDNF or NTN that induces Ret oligomerization and autophosphorylation. Full morphological differentiation of neuroblastoma cells by these neurotrophic factors was also Ca2+-dependent. These findings thus suggested that, in addition to GPI-linked cell surface proteins, Ca2+ ions are components of the signal transducing complex formed by Ret and GDNF protein family.
AB - Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) define a new family of neurotrophic factors that play crucial roles in survival and differentiation of various neurons. Recent studies demonstrated that GDNF and NTN use a multicomponent receptor system in which glycosol-phosphatidylinositol (GPI)-linked cell surface proteins and Ret receptor tyrosine kinase function as the ligand-binding and signalling components, respectively. In the present study, we investigated the role of Ca2+ ions for biochemical and biological activities of Ret because Ret has a unique structure of the extracellular domain with the cadherin-like motif. The results demonstrated that Ca2+ ions might be required for the complex formation of Ret and GDNF or NTN that induces Ret oligomerization and autophosphorylation. Full morphological differentiation of neuroblastoma cells by these neurotrophic factors was also Ca2+-dependent. These findings thus suggested that, in addition to GPI-linked cell surface proteins, Ca2+ ions are components of the signal transducing complex formed by Ret and GDNF protein family.
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U2 - 10.1038/sj.onc.1201548
DO - 10.1038/sj.onc.1201548
M3 - Article
C2 - 9467954
AN - SCOPUS:0032556951
SN - 0950-9232
VL - 16
SP - 293
EP - 299
JO - Oncogene
JF - Oncogene
IS - 3
ER -
