ArticleMolecular and cellular biology2002
The carboxyl-terminal domain of the protein kinase fused can function as a dominant inhibitor of hedgehog signaling.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- The small GTPase Rap1 is a modulator of Hedgehog signaling.Developmental biology · 2016Article
- Contributions of Costal 2-Fused interactions to Hedgehog signaling in Drosophila.Development (Cambridge, England) · 2015Article
- A Comparison of Ci/Gli Activity as Regulated by Sufu in Drosophila and Mammalian Hedgehog Response.PloS one · 2015Article
- The extracellular loops of Smoothened play a regulatory role in control of Hedgehog pathway activation.Development (Cambridge, England) · 2012Article
- Hedgehog activates fused through phosphorylation to elicit a full spectrum of pathway responses.Developmental cell · 2011Article
- Dual function of UNC-51-like kinase 3 (Ulk3) in the Sonic hedgehog signaling pathway.The Journal of biological chemistry · 2010Article
- A quantification of pathway components supports a novel model of Hedgehog signal transduction.The Journal of biological chemistry · 2009Article
- G protein Galphai functions immediately downstream of Smoothened in Hedgehog signalling.Nature · 2008Article
- Costal2 functions as a kinesin-like protein in the hedgehog signal transduction pathway.Current biology : CB · 2008Article
- The role of kinases in the Hedgehog signalling pathway.EMBO reports · 2008Review
- Smoothened regulates activator and repressor functions of Hedgehog signaling via two distinct mechanisms.The Journal of biological chemistry · 2006Article
- A genome-wide RNA interference screen in Drosophila melanogaster cells for new components of the Hh signaling pathway.Nature genetics · 2005Article
- Mice deficient in the fused homolog do not exhibit phenotypes indicative of perturbed hedgehog signaling during embryonic development.Molecular and cellular biology · 2005Article
- An intramolecular association between two domains of the protein kinase Fused is necessary for Hedgehog signaling.Molecular and cellular biology · 2004Article
- Suppressor of fused regulates Gli activity through a dual binding mechanism.Molecular and cellular biology · 2004Article
- Regulation of Hedgehog signaling: a complex story.Biochemical pharmacology · 2004Review
- The Kinesin-related protein Costal2 associates with membranes in a Hedgehog-sensitive, Smoothened-independent manner.The Journal of biological chemistry · 2004Article
- Identification of a functional interaction between the transmembrane protein Smoothened and the kinesin-related protein Costal2.Current biology : CB · 2003Article
- Smoothened transduces Hedgehog signal by physically interacting with Costal2/Fused complex through its C-terminal tail.Genes & development · 2003Article
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Authors and funding
5 authors.
Funding
Abstract
The secreted protein hedgehog (Hh) plays a critical role in the developmental patterning of multiple tissues. In Drosophila melanogaster, a cytosolic multiprotein signaling complex appears necessary for Hh signaling. Genes that encode components of this Hh signaling complex (HSC) were originally identified and characterized based on their genetic interactions with hh, as well as with each other. It is only in recent years that the mechanistic functions of these components have begun to be unraveled. Here, we have investigated the relationship between two components of the HSC, the serine/threonine protein kinase Fused (Fu) and the kinesin-related protein Costal2 (Cos2). We have reconstituted a Fu/Cos2 complex in vitro and shown that Fu is able to directly associate with Cos2, forming a complex whose molecular size is similar to a previously described complex found in Drosophila cell extracts. We have also determined that the carboxyl-terminal domain of Fu is necessary and sufficient for the direct binding of Fu to Cos2. To validate the physiological relevance of this interaction, we overexpressed the carboxyl-terminal domain of Fu in wild-type flies. These flies exhibit a phenotype similar to that seen in fu mutants and consistent with an hh loss-of-function phenotype. We conclude that the carboxyl-terminal domain of Fu can function in a dominant negative manner, by preventing endogenous Fu from binding to Cos2. Thus, we provide the first evidence that Hh signaling can be compromised by targeting the HSC for disruption.
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