A phosphorylation site in the Ftz homeodomain is required for activity

Jianli Dong, Ling Hong Hung, Robert Strome, Henry M. Krause

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The Drosophila homeodomain-containing protein Fushi tarazu (Ftz) is expressed sequentially in the embryo, first in alternate segments, then in specific neuroblasts and neurons in the central nervous system, and finally in parts of the gut. During these different developmental stages, the protein is heavily phosphorylated on different subsets of Ser and Thr residues. This stage-specific phosphorylation suggests possible roles for signal transduction pathways in directing tissue-specific Ftz activities. Here we show that one of the Ftz phosphorylation sites, T263 in the N-terminus of the Ftz homeodomain, is phosphorylated in vitro by Drosophila embryo extracts and protein kinase A. In the embryo, mutagenesis of this site to the non-phosphorylatable residue Ala resulted in loss of ftz-dependent segments. Conversely, substitution of T263 with Asp, which is also non-phosphorylatable, but which successfully mimics phosphorylated residues in a number of proteins, rescued the mutant phenotype. This suggests that T263 is in the phosphorylated state when functioning normally in vivo. We also demonstrate that the T263 substitutions of Ala and Asp do not affect Ftz DNA-binding activity in vitro, nor do they affect stability or transcriptional activity in transfected S2 cells. This suggests that T263 phosphorylation is most likely required for a homeodomain-mediated interaction with an embryonically expressed protein.

Original languageEnglish (US)
Pages (from-to)2308-2318
Number of pages11
JournalEMBO Journal
Volume17
Issue number8
DOIs
StatePublished - Apr 15 1998
Externally publishedYes

Fingerprint

Phosphorylation
Embryonic Structures
Viperidae
Fushi Tarazu Transcription Factors
Substitution reactions
Drosophila Proteins
Homeodomain Proteins
Signal transduction
Mutagenesis
Neurology
Mutant Proteins
Cyclic AMP-Dependent Protein Kinases
Drosophila
Neurons
Signal Transduction
Proteins
Central Nervous System
Tissue
Phenotype
DNA

Keywords

  • cAMP-dependent protein kinase
  • Drosophila
  • Fushi tarazu
  • Homeodomain
  • Phosphorylation

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

A phosphorylation site in the Ftz homeodomain is required for activity. / Dong, Jianli; Hung, Ling Hong; Strome, Robert; Krause, Henry M.

In: EMBO Journal, Vol. 17, No. 8, 15.04.1998, p. 2308-2318.

Research output: Contribution to journalArticle

Dong, Jianli ; Hung, Ling Hong ; Strome, Robert ; Krause, Henry M. / A phosphorylation site in the Ftz homeodomain is required for activity. In: EMBO Journal. 1998 ; Vol. 17, No. 8. pp. 2308-2318.
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