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Gene Review

cos  -  costa

Drosophila melanogaster

Synonyms: CG1708, COS2, COS[2], Cos, Cos-2, ...
 
 
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Disease relevance of cos

  • We also demonstrate that the phosphorylation pattern of Cos2 produced by baculovirus coexpression with kinase-dead Fu is almost identical to the phosphorylation pattern of Cos2 isolated from unstimulated S2 cells [1].
  • We previously showed that NTA was able to induce aneuploidy (chromosomal gain) in the germ cells of both Drosophila and the mouse when tested at the exposure levels of 5 x 10(-2) M and 275 mg per kg body weight, respectively [Costa et al., Environ Mol Mutagen 12:397-407, 1988] [2].
  • BACKGROUND: Autosomal dominant, nonsyndromic, hereditary hearing impairment in a large Costa Rican kindred is caused by a mutation in the human homolog of the Drosophila diaphanous gene [3].
 

High impact information on cos

  • Hedgehog elicits signal transduction by means of a large complex containing the kinesin-related protein costal2 [4].
  • Taken together, our results suggest that Smo transduces the Hh signal by physically interacting with the Cos2/Fu protein complex [5].
  • We show that Cos2 binds Ci, prevents its nuclear import, and inhibits its activity via this domain [6].
  • Differential regulation of Hedgehog target gene transcription by Costal2 and Suppressor of Fused [7].
  • A point mutation in the motor domain of Cos2 results in a dominant-negative form of the protein that derepresses dpp but not ptc [7].
 

Chemical compound and disease context of cos

 

Biological context of cos

  • Here we identified and characterized human ortholog of Drosophila Cos2 by using bioinformatics [8].
  • Hedgehog signal transduction via Smoothened association with a cytoplasmic complex scaffolded by the atypical kinesin, Costal-2 [9].
  • We then show that the primary Fu-induced phosphorylation site of Cos2 is serine 572, whereas serine 931 is phosphorylated to a lesser extent [1].
  • An unregulated FuII protein, which can be limited to the 80 N-terminal amino acids of the kinase domain, would be responsible for the neomorphic costal-2 phenotype displayed by the fuII-Su(fu) interaction [10].
  • Mosaic analyses show that the duplications arise nonautonomously in the larval stages but that the costal-2 gene is not required after early embryogenesis [11].
 

Anatomical context of cos

  • In response to Hh and through interaction with Cos2, Smo mediates both inhibition of the endosome-associated HSC-R and activation of HSC-A at the plasma membrane [12].
  • We demonstrate that Cos2 is capable of tethering an exogenous protein to vesicular membranes and that Cos2 association with membranes is Hh-sensitive [12].
  • Fu, Cos-2 and Ci are co-associated in vivo in large complexes that are bound to microtubules in a Hh-dependent manner [6,7] [13].
 

Associations of cos with chemical compounds

  • Mutation of serine 572 to alanine eliminates most, but not all, specific phosphopeptides of Cos2 when coexpressed with Fu [1].
 

Physical interactions of cos

  • We also show that Cos2 binding on Smo is necessary for the Hh-dependent dissociation of Ci from this complex [14].
  • Moreover, overexpressing Cos2 mutants that fail to bind Fu and Ci but retain Smo-binding activity blocks Hh signaling [5].
 

Enzymatic interactions of cos

  • We propose that Cos2 recruits multiple kinases to efficiently phosphorylate Ci and that Hh inhibits Ci phosphorylation by specifically interfering with kinase recruitment [15].
 

Regulatory relationships of cos

 

Other interactions of cos

  • The HSC consists of the Kinesin Related Protein, Costal2 (Cos2), the serine-threonine protein kinase [16].
  • Deletion of the Cos2/Fu-binding domain from Smo abolishes its signaling activity [5].
  • Repression of ptc in the presence of the dominant-negative form of Cos2 requires Su(fu), which is phosphorylated in response to Hh in vivo [7].
  • Dominant gain of function alleles at the Costal-1 locus are also described and data are presented that argue that these are neomorphic and act in trans to impair functioning of costal-2 [17].
  • Genetic and cytogenetic analysis of the 43A-E region containing the segment polarity gene costa and the cellular polarity genes prickle and spiny-legs in Drosophila melanogaster [18].
 

Analytical, diagnostic and therapeutic context of cos

References

  1. Hedgehog-stimulated phosphorylation of the kinesin-related protein Costal2 is mediated by the serine/threonine kinase fused. Nybakken, K.E., Turck, C.W., Robbins, D.J., Bishop, J.M. J. Biol. Chem. (2002) [Pubmed]
  2. A concerted approach to the study of the aneuploidogenic properties of two chelating agents (EDTA and NTA) in the germ and somatic cell lines of Drosophila and the mouse. Zordan, M., Russo, A., Costa, R., Bianco, N., Beltrame, C., Levis, A.G. Environ. Mol. Mutagen. (1990) [Pubmed]
  3. Further characterization of the DFNA1 audiovestibular phenotype. Lalwani, A.K., Jackler, R.K., Sweetow, R.W., Lynch, E.D., Raventós, H., Morrow, J., King, M.C., León, P.E. Arch. Otolaryngol. Head Neck Surg. (1998) [Pubmed]
  4. Hedgehog elicits signal transduction by means of a large complex containing the kinesin-related protein costal2. Robbins, D.J., Nybakken, K.E., Kobayashi, R., Sisson, J.C., Bishop, J.M., Thérond, P.P. Cell (1997) [Pubmed]
  5. Smoothened transduces Hedgehog signal by physically interacting with Costal2/Fused complex through its C-terminal tail. Jia, J., Tong, C., Jiang, J. Genes Dev. (2003) [Pubmed]
  6. Interactions with Costal2 and suppressor of fused regulate nuclear translocation and activity of cubitus interruptus. Wang, G., Amanai, K., Wang, B., Jiang, J. Genes Dev. (2000) [Pubmed]
  7. Differential regulation of Hedgehog target gene transcription by Costal2 and Suppressor of Fused. Ho, K.S., Suyama, K., Fish, M., Scott, M.P. Development (2005) [Pubmed]
  8. KIF27 is one of orthologs for Drosophila Costal-2. Katoh, Y., Katoh, M. Int. J. Oncol. (2004) [Pubmed]
  9. Hedgehog signal transduction via Smoothened association with a cytoplasmic complex scaffolded by the atypical kinesin, Costal-2. Lum, L., Zhang, C., Oh, S., Mann, R.K., von Kessler, D.P., Taipale, J., Weis-Garcia, F., Gong, R., Wang, B., Beachy, P.A. Mol. Cell (2003) [Pubmed]
  10. Functional domains of fused, a serine-threonine kinase required for signaling in Drosophila. Thérond, P., Alves, G., Limbourg-Bouchon, B., Tricoire, H., Guillemet, E., Brissard-Zahraoui, J., Lamour-Isnard, C., Busson, D. Genetics (1996) [Pubmed]
  11. The segment polarity gene costal-2 in Drosophila. II. The origin of imaginal pattern duplications. Simpson, P., Grau, Y. Dev. Biol. (1987) [Pubmed]
  12. The Kinesin-related protein Costal2 associates with membranes in a Hedgehog-sensitive, Smoothened-independent manner. Stegman, M.A., Goetz, J.A., Ascano, M., Ogden, S.K., Nybakken, K.E., Robbins, D.J. J. Biol. Chem. (2004) [Pubmed]
  13. Suppressor of fused links fused and Cubitus interruptus on the hedgehog signalling pathway. Monnier, V., Dussillol, F., Alves, G., Lamour-Isnard, C., Plessis, A. Curr. Biol. (1998) [Pubmed]
  14. Stability and association of Smoothened, Costal2 and Fused with Cubitus interruptus are regulated by Hedgehog. Ruel, L., Rodriguez, R., Gallet, A., Lavenant-Staccini, L., Thérond, P.P. Nat. Cell Biol. (2003) [Pubmed]
  15. Hedgehog-regulated Costal2-kinase complexes control phosphorylation and proteolytic processing of Cubitus interruptus. Zhang, W., Zhao, Y., Tong, C., Wang, G., Wang, B., Jia, J., Jiang, J. Dev. Cell (2005) [Pubmed]
  16. Regulation of Hedgehog signaling: a complex story. Ogden, S.K., Ascano, M., Stegman, M.A., Robbins, D.J. Biochem. Pharmacol. (2004) [Pubmed]
  17. The segment polarity gene costal-2 in Drosophila. I. The organization of both primary and secondary embryonic fields may be affected. Grau, Y., Simpson, P. Dev. Biol. (1987) [Pubmed]
  18. Genetic and cytogenetic analysis of the 43A-E region containing the segment polarity gene costa and the cellular polarity genes prickle and spiny-legs in Drosophila melanogaster. Heitzler, P., Coulson, D., Saenz-Robles, M.T., Ashburner, M., Roote, J., Simpson, P., Gubb, D. Genetics (1993) [Pubmed]
  19. Segmental polarity in Drosophila melanogaster: genetic dissection of fused in a Suppressor of fused background reveals interaction with costal-2. Préat, T., Thérond, P., Limbourg-Bouchon, B., Pham, A., Tricoire, H., Busson, D., Lamour-Isnard, C. Genetics (1993) [Pubmed]
 
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