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The signaling adapters fibroblast growth factor receptor substrate 2 and 3 are activated by the thyroid TRK

Valeria Ranzi1, Susan O Meakin, Claudia Miranda

  • 1Department of Experimental Oncology, Operative Unit Molecular Mechanisms of Cancer Growth and Progression, Istituto Nazionale Tumori, 20133 Milan, Italy.

Endocrinology
|February 15, 2003
PubMed

Insights

Thyroid TRK oncogenes activate fibroblast growth factor receptor substrates (FRS)2 and FRS3. Differential expression of FRS2 in tumors suggests a role in thyroid carcinogenesis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Signal Transduction

Background:

  • Thyroid TRK oncogenes arise from chromosomal rearrangements involving the neurotrophic tyrosine receptor kinase type 1 (NTRK1).
  • TRK oncoproteins exhibit constitutive tyrosine kinase activity, leading to NIH3T3 cell transformation.
  • Signaling pathways of TRK oncoproteins involve transducers activated by the NGF-stimulated NTRK1 receptor.

Purpose of the Study:

  • Investigate the role of fibroblast growth factor receptor substrates (FRS)2 and FRS3 in the signaling of thyroid TRK-T1 and TRK-T3 oncogenes.
  • Determine if FRS2 and FRS3 are recruited and activated by TRK-T1 and TRK-T3.
  • Analyze the expression patterns of FRS adapters in normal and tumor thyroid tissues.

Main Methods:

  • In vitro and in vivo assays to assess FRS2 and FRS3 recruitment and activation by TRK oncogenes.
  • Interaction studies using TRK-T3 mutants to identify recruitment sites.
  • Expression analysis of FRS adapters in normal and tumor thyroid samples.

Main Results:

  • Both FRS2 and FRS3 are recruited and activated by the thyroid TRK-T1 and TRK-T3 oncogenes.
  • FRS3 is recruited via the same tyrosine residue as Shc and FRS2.
  • FRS3 is expressed in both normal and tumor thyroid tissues, while FRS2 is absent in normal thyroid but differentially expressed in some tumors.

Conclusions:

  • FRS2 and FRS3 adapter proteins are involved in the signaling of thyroid TRK oncogenes.
  • The differential expression of FRS2 in thyroid tumors suggests its potential involvement in thyroid carcinogenesis.
  • These findings highlight the role of FRS adapters in TRK-driven thyroid cancer.

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