ULK3:SUFU dissociates

Stable Identifier
R-HSA-5635839
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

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
19305393 Fused has evolved divergent roles in vertebrate Hedgehog signalling and motile ciliogenesis

Wilson, CW, Nguyen, CT, Chen, MH, Yang, JH, Gacayan, R, Huang, J, Chen, JN, Chuang, PT

Nature 2009
22391301 Mammalian homologues of Drosophila fused kinase

Maloverjan, A, Piirsoo, M

Vitam. Horm. 2012
20643644 Dual function of UNC-51-like kinase 3 (Ulk3) in the Sonic hedgehog signaling pathway

Maloverjan, A, Piirsoo, M, Kasak, L, Peil, L, Østerlund, T, Kogerman, P

J. Biol. Chem. 2010
23719536 The mechanisms of Hedgehog signalling and its roles in development and disease

Briscoe, J, Thérond, PP

Nat. Rev. Mol. Cell Biol. 2013
19878745 Identification of a novel serine/threonine kinase ULK3 as a positive regulator of Hedgehog pathway

Maloverjan, A, Piirsoo, M, Michelson, P, Kogerman, P, Osterlund, T

Exp. Cell Res. 2010
Participants
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