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Link to original content: http://www.ncbi.nlm.nih.gov/pubmed/19878745
Identification of a novel serine/threonine kinase ULK3 as a positive regulator of Hedgehog pathway - PubMed Skip to main page content
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. 2010 Feb 15;316(4):627-37.
doi: 10.1016/j.yexcr.2009.10.018. Epub 2009 Oct 21.

Identification of a novel serine/threonine kinase ULK3 as a positive regulator of Hedgehog pathway

Alla Maloverjan  1 , Marko Piirsoo, Piret Michelson, Priit Kogerman, Torben Osterlund
Affiliations

Identification of a novel serine/threonine kinase ULK3 as a positive regulator of Hedgehog pathway

Alla Maloverjan et al. Exp Cell Res. .

Abstract

The Hedgehog (Hh) signaling pathway plays crucial roles in embryonic development and is implicated in tissue homeostasis maintenance and neurogenesis in adults. Aberrant activation of Hh signaling is associated with various developmental abnormalities and several types of cancer. Genetic and biochemical studies ascertain serine/threonine kinase Fused (Fu) as a protein involved in Hh signaling in Drosophila. However, the role of Fu is not fully conserved in mammals suggesting involvement of other kinases in the mammalian Hh signaling pathway. In search of potential homologues to Drosophila and human Fu, we have cloned human serine/threonine kinase ULK3 and assessed its ability to regulate GLI transcription factors, mediators of SHH signaling. We demonstrate that ULK3 enhances endogenous and over-expressed GLI1 and GLI2 transcriptional activity in cultured cells, as assessed by GLI-luciferase reporter assay. Besides that, ULK3 alters subcellular localization of GLI1, as assessed by immunofluorescent staining and immunoblotting assays. We show that ULK3 is an autophosphorylated kinase and phosphorylates GLI proteins in vitro. We also demonstrate that ULK3 catalytical activity is crucial for its function in SHH pathway. We show that ULK3 is widely expressed and its expression is higher in a number of tissues where Shh signaling is known to be active. Our data suggest that serine/threonine kinase ULK3 is involved in the SHH pathway as a positive regulator of GLI proteins.

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