8srm

Structural highlights

Function

ULK1_HUMAN Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity. May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences. Plays a role early in neuronal differentiation and is required for granule cell axon formation.^{[1] [2] [3]}

See Also

• Serine/threonine protein kinase 3D structures

References

1. ↑ Chan EY, Longatti A, McKnight NC, Tooze SA. Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-terminal domains using an Atg13-independent mechanism. Mol Cell Biol. 2009 Jan;29(1):157-71. doi: 10.1128/MCB.01082-08. Epub 2008 Oct, 20. PMID:18936157 doi:http://dx.doi.org/10.1128/MCB.01082-08
2. ↑ Loffler AS, Alers S, Dieterle AM, Keppeler H, Franz-Wachtel M, Kundu M, Campbell DG, Wesselborg S, Alessi DR, Stork B. Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop. Autophagy. 2011 Jul;7(7):696-706. Epub 2011 Jul 1. PMID:21460634
3. ↑ Jung CH, Seo M, Otto NM, Kim DH. ULK1 inhibits the kinase activity of mTORC1 and cell proliferation. Autophagy. 2011 Oct;7(10):1212-21. doi: 10.4161/auto.7.10.16660. Epub 2011 Oct 1. PMID:21795849 doi:http://dx.doi.org/10.4161/auto.7.10.16660