Hedgehog signal transduction via Smoothened association with a cytoplasmic complex scaffolded by the atypical kinesin, Costal-2

Lawrence Lum; Chi Zhang; Sekyung Oh; Randall K Mann; Doris P von Kessler; Jussi Taipale; Frances Weis-Garcia; Ruoyu Gong; Baolin Wang; Philip A Beachy

doi:10.1016/s1097-2765(03)00426-x

Hedgehog signal transduction via Smoothened association with a cytoplasmic complex scaffolded by the atypical kinesin, Costal-2

Mol Cell. 2003 Nov;12(5):1261-74. doi: 10.1016/s1097-2765(03)00426-x.

Authors

Lawrence Lum¹, Chi Zhang, Sekyung Oh, Randall K Mann, Doris P von Kessler, Jussi Taipale, Frances Weis-Garcia, Ruoyu Gong, Baolin Wang, Philip A Beachy

Affiliation

¹ Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.

PMID: 14636583
DOI: 10.1016/s1097-2765(03)00426-x

Abstract

The seven-transmembrane protein Smoothened (Smo) transduces extracellular activation of the Hedgehog (Hh) pathway by an unknown mechanism to increase transcriptional activity of the latent cytoplasmic transcription factor Ci (Cubitus interruptus). Here, we present evidence that Smo associates directly with a Ci-containing complex that is scaffolded and stabilized by the atypical kinesin, Costal-2 (Cos2). This complex constitutively suppresses pathway activity, but Hh signaling reverses its regulatory effect to promote Ci-mediated transcription. In response to Hh activation of Smo, Cos2 mediates accumulation and phosphorylation of Smo at the membrane as well as phosphorylation of the cytoplasmic components Fu and Su(fu). Positive response of Cos2 to Hh stimulation requires a portion of the Smo cytoplasmic tail and the Cos2 cargo domain, which interacts directly with Smo.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Amino Acid Sequence
Animals
Cell Line
Cytoplasm / chemistry
Cytoplasm / metabolism
DNA-Binding Proteins / metabolism
Drosophila Proteins / genetics
Drosophila Proteins / metabolism*
Drosophila melanogaster / genetics
Drosophila melanogaster / physiology
Embryonic Structures / anatomy & histology
Embryonic Structures / physiology
Gene Expression Regulation, Developmental
Genes, Reporter
Hedgehog Proteins
Humans
Kinesins / genetics
Kinesins / metabolism*
Macromolecular Substances
Molecular Sequence Data
Phosphorylation
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism
RNA Interference
Receptors, G-Protein-Coupled / genetics
Receptors, G-Protein-Coupled / metabolism*
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Repressor Proteins / genetics
Repressor Proteins / metabolism
Sequence Alignment
Signal Transduction / physiology*
Smoothened Receptor
Transcription Factors

Substances

DNA-Binding Proteins
Drosophila Proteins
Hedgehog Proteins
Macromolecular Substances
Receptors, G-Protein-Coupled
Recombinant Fusion Proteins
Repressor Proteins
SMO protein, human
SUFU protein, human
Smoothened Receptor
Su(fu) protein, Drosophila
Transcription Factors
ci protein, Drosophila
cos protein, Drosophila
smo protein, Drosophila
hh protein, Drosophila
fu protein, Drosophila
Protein Serine-Threonine Kinases
Kinesins