Engineering the recruitment of phosphotyrosine binding domain-containing adaptor proteins reveals distinct roles for RET receptor-mediated cell survival

T. Kalle Lundgren, Rizaldy P. Scott, Matthew Smith, Tony Pawson, Patrik Ernfors*

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The RET receptor tyrosine kinase is important for several different biological functions during development. The recruitment at the phosphorylated Tyr1062 site in RET of a number of different phosphotyrosine binding (PTB) domain-containing adaptor proteins, including Shc and Frs2, plays a dominant role for the multiple different biological functions of the RET receptor during development, including stimulation of cell survival. Here, we demonstrate that a competitive recruitment of Shc as opposed to Frs2 mediates the survival signaling arising from RET activation. Based on results from a peptide array, we have genetically engineered the PTB domain binding site of RET to rewire its recruitment of the PTB proteins Shc and Frs2. An engineered RET that has a competitive interaction with Shc at the expense of Frs2, but not a RET receptor that only recruits Frs2, activates cell survival signaling pathways and is protective from cell death in neuronal SK-N-MC cells. Thus, cell type-specific functions involve a competitive recruitment of different PTB adaptor molecules by RET that activate selective signaling pathways.

Original languageEnglish (US)
Pages (from-to)29886-29896
Number of pages11
JournalJournal of Biological Chemistry
Volume281
Issue number40
DOIs
StatePublished - Oct 6 2006

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Engineering the recruitment of phosphotyrosine binding domain-containing adaptor proteins reveals distinct roles for RET receptor-mediated cell survival'. Together they form a unique fingerprint.

Cite this