Structural highlights
Function
[ULK3_HUMAN] Serine/threonine protein kinase that acts as a regulator of Sonic hedgehog (SHH) signaling and autophagy. Acts as a negative regulator of SHH signaling in the absence of SHH ligand: interacts with SUFU, thereby inactivating the protein kinase activity and preventing phosphorylation of GLI proteins (GLI1, GLI2 and/or GLI3). Positively regulates SHH signaling in the presence of SHH: dissociates from SUFU, autophosphorylates and mediates phosphorylation of GLI2, activating it and promoting its nuclear translocation. Phosphorylates in vitro GLI2, as well as GLI1 and GLI3, although less efficiently. Also acts as a regulator of autophagy: following cellular senescence, able to induce autophagy.[1] [2] [3]
References
- ↑ Young AR, Narita M, Ferreira M, Kirschner K, Sadaie M, Darot JF, Tavare S, Arakawa S, Shimizu S, Watt FM, Narita M. Autophagy mediates the mitotic senescence transition. Genes Dev. 2009 Apr 1;23(7):798-803. doi: 10.1101/gad.519709. Epub 2009 Mar 11. PMID:19279323 doi:http://dx.doi.org/10.1101/gad.519709
- ↑ Maloverjan A, Piirsoo M, Michelson P, Kogerman P, Osterlund T. Identification of a novel serine/threonine kinase ULK3 as a positive regulator of Hedgehog pathway. Exp Cell Res. 2010 Feb 15;316(4):627-37. doi: 10.1016/j.yexcr.2009.10.018. Epub, 2009 Oct 21. PMID:19878745 doi:http://dx.doi.org/10.1016/j.yexcr.2009.10.018
- ↑ Maloverjan A, Piirsoo M, Kasak L, Peil L, Osterlund T, Kogerman P. Dual function of UNC-51-like kinase 3 (Ulk3) in the Sonic hedgehog signaling pathway. J Biol Chem. 2010 Sep 24;285(39):30079-90. doi: 10.1074/jbc.M110.133991. Epub, 2010 Jul 19. PMID:20643644 doi:http://dx.doi.org/10.1074/jbc.M110.133991
