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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
Gene Review

brk  -  brinker

Drosophila melanogaster

Synonyms: Brk, CG9653, Dm brk, Dmel\CG9653, ssg-1
 
 
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High impact information on brk

  • Furthermore, we present genetic and biochemical evidence that the brk silencer serves as a direct target for a protein complex consisting of the Smad homologs Mad/Medea and the zinc finger protein Schnurri [1].
  • We then dissect the brk regulatory region and identify two separable elements with opposite properties, a constitutive enhancer and a Dpp morphogen-regulated silencer [1].
  • Throughout development, Dpp transduction causes the graded transcriptional downregulation of the brinker (brk) gene [1].
  • However, here we demonstrate that Dpp can also control gene expression indirectly by downregulating the expression of the brinker gene, which encodes a putative transcription factor that functions to repress Dpp targets [2].
  • We propose that slow-proliferating cells upregulate Brk levels owing to a disadvantage in competing for, or in transducing, the Dpp survival signal [3].
 

Biological context of brk

 

Anatomical context of brk

  • Brk is expressed by most of the oocyte associated follicle cells, starting from stage 8 of oogenesis [7].
  • Some of these thresholds depend on a putative repressor, Brinker, which is expressed in the neurogenic ectoderm in response to the maternal Dorsal gradient and Dpp signaling [8].
  • The salivary gland placode in brinker mutants appears reduced along both the anterior-posterior and dorso-ventral axis [9].
  • Brk also functions as a rapid downstream signaling intermediate following calcium-induced differentiation in keratinocytes [10].
 

Associations of brk with chemical compounds

  • Several Brk family kinases have an inhibitory effect on Ras pathway signaling from receptor tyrosine kinases [10].
 

Physical interactions of brk

 

Regulatory relationships of brk

  • For target genes to be activated, Dpp signalling must suppress transcription of a repressor encoded by the brinker (brk) gene [12].
  • Mosaic analysis indicates that brk-expressing cells produce a short-range signal that can induce vein formation in adjacent omb-expressing cells [13].
  • Furthermore, Brinker blocks transcriptional activation by ubiquitous Wg signaling [14].
 

Other interactions of brk

  • These results suggest that the Sog inhibitor and Brk repressor work in concert to establish sharp dorsolateral limits of gene expression [15].
  • Using this omb wing enhancer, we show that Brk is a sequence-specific DNA binding protein [11].
  • This suggests that Brinker may have a widespread function in antagonizing Wg signaling [14].
  • Finally, brinker and tsh produce similar mutant phenotypes in the ventral epidermis, and double mutants mimic overactive Wg signaling in this tissue [14].
  • Here, we show that Wg-mediated repression of Ubx B depends on Brinker, which binds to the WRS-R [14].

References

  1. Conversion of an extracellular Dpp/BMP morphogen gradient into an inverse transcriptional gradient. Müller, B., Hartmann, B., Pyrowolakis, G., Affolter, M., Basler, K. Cell (2003) [Pubmed]
  2. Transducing the Dpp morphogen gradient in the wing of Drosophila: regulation of Dpp targets by brinker. Campbell, G., Tomlinson, A. Cell (1999) [Pubmed]
  3. Cells compete for decapentaplegic survival factor to prevent apoptosis in Drosophila wing development. Moreno, E., Basler, K., Morata, G. Nature (2002) [Pubmed]
  4. The transcription factor Schnurri plays a dual role in mediating Dpp signaling during embryogenesis. Torres-Vazquez, J., Park, S., Warrior, R., Arora, K. Development (2001) [Pubmed]
  5. Schnurri transcription factors from Drosophila and vertebrates can mediate Bmp signaling through a phylogenetically conserved mechanism. Yao, L.C., Blitz, I.L., Peiffer, D.A., Phin, S., Wang, Y., Ogata, S., Cho, K.W., Arora, K., Warrior, R. Development (2006) [Pubmed]
  6. Repression of dpp targets by binding of brinker to mad sites. Kirkpatrick, H., Johnson, K., Laughon, A. J. Biol. Chem. (2001) [Pubmed]
  7. The role of brinker in eggshell patterning. Chen, Y., Schüpbach, T. Mech. Dev. (2006) [Pubmed]
  8. Brinker is a sequence-specific transcriptional repressor in the Drosophila embryo. Zhang, H., Levine, M., Ashe, H.L. Genes Dev. (2001) [Pubmed]
  9. Analysis of Drosophila salivary gland, epidermis and CNS development suggests an additional function of brinker in anterior-posterior cell fate specification. Lammel, U., Meadows, L., Saumweber, H. Mech. Dev. (2000) [Pubmed]
  10. Brk, Srm, Frk, and Src42A form a distinct family of intracellular Src-like tyrosine kinases. Serfas, M.S., Tyner, A.L. Oncol. Res. (2003) [Pubmed]
  11. Direct transcriptional control of the Dpp target omb by the DNA binding protein Brinker. Sivasankaran, R., Vigano, M.A., Müller, B., Affolter, M., Basler, K. EMBO J. (2000) [Pubmed]
  12. Schnurri mediates Dpp-dependent repression of brinker transcription. Marty, T., Müller, B., Basler, K., Affolter, M. Nat. Cell Biol. (2000) [Pubmed]
  13. brinker and optomotor-blind act coordinately to initiate development of the L5 wing vein primordium in Drosophila. Cook, O., Biehs, B., Bier, E. Development (2004) [Pubmed]
  14. The transcriptional repressor Brinker antagonizes Wingless signaling. Saller, E., Kelley, A., Bienz, M. Genes Dev. (2002) [Pubmed]
  15. Dpp signaling thresholds in the dorsal ectoderm of the Drosophila embryo. Ashe, H.L., Mannervik, M., Levine, M. Development (2000) [Pubmed]
 
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