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Intracellular RET signaling pathways activated by GDNF

Kumi Kawai1, Masahide Takahashi2,3

  • 1Department of Pathology, Fujita Health University, 1-98 Kutsukake-cho, Dengakugakubo, Toyoake, 470-1192, Japan.

Cell and Tissue Research
|August 21, 2020
PubMed

Insights

Activation of the REarranged during Transfection (RET) proto-oncogene drives human cancers. This review summarizes how glial cell line-derived neurotrophic factor (GDNF) signaling activates RET intracellularly, impacting cancer and development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • The REarranged during Transfection (RET) proto-oncogene is implicated in various human cancers, including thyroid and lung carcinomas.
  • RET activation in tumors often results from mutations or rearrangements, leading to constitutive tyrosine kinase activity.

Purpose of the Study:

  • To review the physiological activation of RET by glial cell line-derived neurotrophic factor (GDNF) ligands.
  • To discuss the significance of intracellular RET signaling pathways in both normal development and disease.

Main Methods:

  • Literature review of studies on RET proto-oncogene activation.
  • Analysis of signaling pathways involving GDNF, GFRαs, and RET.
  • Examination of the role of tyrosine phosphorylation and adaptor protein recruitment.

Main Results:

  • Physiological RET activation occurs via GDNF binding to GFRα coreceptors, promoting RET dimerization.
  • GDNF-GFRα1-RET signaling is vital for the development of the enteric nervous system, kidney, and spermatogenesis.
  • Intracellular tyrosine phosphorylation of RET and subsequent adaptor protein recruitment are critical for biological functions.

Conclusions:

  • Understanding RET signaling is crucial for comprehending its role in human cancers.
  • The review highlights the dual role of RET signaling in development and oncogenesis.
  • Further research into RET pathways may yield novel therapeutic strategies.
Keywords:
GDNFGDNF family receptor αIntracellular signalingOncogeneRETTyrosine phosphorylation

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