Identification of a Frizzled-like cysteine rich domain in the extracellular region of developmental receptor tyrosine kinases

Jose Saldanha, Juswinder Singh, Daruka Mahadevan

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

In Drosophila, members of the Frizzled family of tissue-polarity genes encode proteins that appear to function as cell-surface receptors for Wnts. The Frizzled genes belong to the seven transmembrane class of receptors (7TMR) and have on their extracellular region a cysteine-rich domain that has been implicated as the Wnt binding domain. This region has a characteristic spacing of ten cysteines, which has also been identified in FrzB (a secreted antagonist of Wnt signaling) and Smoothened (another 7TMR, which is involved in suppression of the hedgehog pathway). We have identified, using BLAST, sequence similarity between the cysteine-rich domain of Frizzled and several receptor tyrosine kinases, which have roles in development. These include the muscle-specific receptor tyrosine kinase (MUSK), the neuronal specific kinase (NSK2), and ROR1 and ROR2. At present, the ligands for these developmental tyrosine kinases are unknown. Our results suggest that Wnt-like ligands may bind to these developmental tyrosine kinases.

Original languageEnglish (US)
Pages (from-to)1632-1635
Number of pages4
JournalProtein Science
Volume7
Issue number7
DOIs
StatePublished - Jul 1998
Externally publishedYes

Keywords

  • Cysteine-rich domains
  • Developmental tyrosine kinases
  • Frizzled
  • Wingless

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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