Sprouty2 regulates growth and differentiation of human neuroblastoma cells through 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

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)815-821
Number of pages7
JournalCancer science
Volume98
Issue number6
DOIs
Publication statusPublished - 06-2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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