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Gene Review

kek1  -  kekkon-1

Drosophila melanogaster

Synonyms: BEST:GM02380, CG12283, CT18186, Dmel\CG12283, Dmkek1, ...
 
 
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High impact information on kek1

  • Consistent with our loss-of-function studies, we demonstrate that ectopic overexpression of kek1 mimics a loss of EGFR activity [1].
  • Furthermore, embryos of some double mutant combinations of neurotactin and other genes encoding adhesion/signaling molecules, including neuroglian, derailed, and kekkon1, displayed phenotypic synergy [2].
  • Broad expression of kekon at the stage in which the follicle cells migrate posteriorly over the oocyte, demonstrates the capacity of the pathway to pattern all follicle cells except the ventral-most rows [3].
  • When lambda top was expressed in all the follicle cells covering the oocyte, kek 1 and argos expression was induced in follicle cells all along the anterior/posterior axis of the egg chamber [4].
  • Leucine-rich repeats and immunoglobulin-like domains-1 (LRIG1) is a transmembrane protein with an ectodomain containing 15 leucine-rich repeats (LRRs) homologous to mammalian decorin and the Drosophila kekkon1 gene [5].
 

Biological context of kek1

  • In D. melanogaster, kek1 is a transcriptional target of EGFR signaling during oogenesis, where it acts to attenuate receptor activity through an inhibitory feedback loop [6].
  • Using a GMR-GAL4, UAS kek1-GFP misexpression phenotype we isolated missense mutations in the kek1 transgene affecting its ability to inhibit EGFR signaling [7].
  • We demonstrate directly, and using a series of Kek1-EGFR chimeras, that Kek1 is not a phosphorylation substrate for the receptor in vivo [8].
  • While this arrangement of domains predicts a possible role as cell adhesion molecules (CAMs), to date little is known about the function or evolutionary relationship of these additional Kek molecules [9].
  • Kek1 contains both leucine-rich repeats (LRRs) and an immunoglobulin (Ig) domain, two of the most prevalent motifs found within metazoan genomes [7].
 

Anatomical context of kek1

  • Both genes are expressed in neurons as they differentiate in the embryonic central nervous system (CNS). kek1 is also expressed in other patterned epithelia, such as the follicle cells of the developing egg chamber, where it is found in a dorsal-ventral gradient around the oocyte [10].
 

Regulatory relationships of kek1

 

Other interactions of kek1

  • Control of bract formation in Drosophila: poxn, kek1, and the EGF-R pathway [11].
  • Here we report that orthologs of Kek1, Kek2, Kek5, and Kek6 exist in the mosquito, Anopheles gambiae, and the honeybee, Apis mellifera, indicating that this family has been conserved for ~300 million years of evolutionary time [9].
  • The coexpression of kek2 in the CNS leads us to suggest that Kek1 is part of a family of cell surface proteins with redundant function [10].

References

  1. The transmembrane molecule kekkon 1 acts in a feedback loop to negatively regulate the activity of the Drosophila EGF receptor during oogenesis. Ghiglione, C., Carraway, K.L., Amundadottir, L.T., Boswell, R.E., Perrimon, N., Duffy, J.B. Cell (1999) [Pubmed]
  2. Neurotactin functions in concert with other identified CAMs in growth cone guidance in Drosophila. Speicher, S., García-Alonso, L., Carmena, A., Martín-Bermudo, M.D., de la Escalera, S., Jiménez, F. Neuron (1998) [Pubmed]
  3. Sequential activation of the EGF receptor pathway during Drosophila oogenesis establishes the dorsoventral axis. Sapir, A., Schweitzer, R., Shilo, B.Z. Development (1998) [Pubmed]
  4. Ectopic activation of torpedo/Egfr, a Drosophila receptor tyrosine kinase, dorsalizes both the eggshell and the embryo. Queenan, A.M., Ghabrial, A., Schüpbach, T. Development (1997) [Pubmed]
  5. A soluble ectodomain of LRIG1 inhibits cancer cell growth by attenuating basal and ligand-dependent EGFR activity. Goldoni, S., Iozzo, R.A., Kay, P., Campbell, S., McQuillan, A., Agnew, C., Zhu, J.X., Keene, D.R., Reed, C.C., Iozzo, R.V. Oncogene (2007) [Pubmed]
  6. Conservation of an inhibitor of the epidermal growth factor receptor, Kekkon1, in dipterans. Derheimer, F.A., MacLaren, C.M., Weasner, B.P., Alvarado, D., Duffy, J.B. Genetics (2004) [Pubmed]
  7. Knockouts of Kekkon1 define sequence elements essential for Drosophila epidermal growth factor receptor inhibition. Alvarado, D., Rice, A.H., Duffy, J.B. Genetics (2004) [Pubmed]
  8. Bipartite inhibition of Drosophila epidermal growth factor receptor by the extracellular and transmembrane domains of Kekkon1. Alvarado, D., Rice, A.H., Duffy, J.B. Genetics (2004) [Pubmed]
  9. Comparative analysis of the Kekkon molecules, related members of the LIG superfamily. MacLaren, C.M., Evans, T.A., Alvarado, D., Duffy, J.B. Dev. Genes Evol. (2004) [Pubmed]
  10. The Drosophila kekkon genes: novel members of both the leucine-rich repeat and immunoglobulin superfamilies expressed in the CNS. Musacchio, M., Perrimon, N. Dev. Biol. (1996) [Pubmed]
  11. Control of bract formation in Drosophila: poxn, kek1, and the EGF-R pathway. Layalle, S., Ragone, G., Giangrande, A., Ghysen, A., Dambly-Chaudière, C. Genesis (2004) [Pubmed]
 
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