Reactome | ULK3:SUFU dissociates

ULK3:SUFU dissociates

Stable Identifier

R-HSA-5635839

Type

Reaction [dissociation]

Species

Homo sapiens

Compartment

cilium

ReviewStatus

5/5

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ULK3 is a serine-threonine kinase that was identified as a positive regulator of Hh signaling that regulates GLI activity by phosphorylating the full-length form (Maloverjan et al, 2010a). In the absence of Hh ligand, ULK3 forms a complex with SUFU that restricts its kinase activity (Maloverjan et al, 2010b). Upon Hh stimulation, the ULK3:SUFU complex dissociates, allowing ULK3 to phosphorylate the full-length GLI proteins and promoting their activation and nuclear localization (Maloverjan et al, 2010a; Maloverjan et al, 2010b). ULK3 is related by sequence to the vertebrate kinase STK36, homologue to Drosophila Fused (Fu). While Fu plays a critical role in propagating Hh signal and is part of the Hedgehog signaling complex (HSC), STK36 is not required for Hh signaling in vertebrate cells but instead contributes to the formation of motile cilia (Wilson et al, 2009; reviewed in Briscoe and Therond, 2013; Maloverjan and Piirsoo, 2012).

Literature References

PubMed ID	Title	Journal	Year
22391301	Mammalian homologues of Drosophila fused kinase Piirsoo, M, Maloverjan, A	Vitam. Horm.	2012
19305393	Fused has evolved divergent roles in vertebrate Hedgehog signalling and motile ciliogenesis Huang, J, Chen, JN, Chuang, PT, Gacayan, R, Yang, JH, Nguyen, CT, Wilson, CW, Chen, MH	Nature	2009
20643644	Dual function of UNC-51-like kinase 3 (Ulk3) in the Sonic hedgehog signaling pathway Kogerman, P, Kasak, L, Piirsoo, M, Maloverjan, A, Østerlund, T, Peil, L	J. Biol. Chem.	2010
23719536	The mechanisms of Hedgehog signalling and its roles in development and disease Thérond, PP, Briscoe, J	Nat. Rev. Mol. Cell Biol.	2013
19878745	Identification of a novel serine/threonine kinase ULK3 as a positive regulator of Hedgehog pathway Kogerman, P, Osterlund, T, Piirsoo, M, Maloverjan, A, Michelson, P	Exp. Cell Res.	2010