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Product Usage Information

Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM NaCl, 100 µg/ml BSA and 50% glycerol. Store at –20°C. Do not aliquot the antibody.

Specificity / Sensitivity

Phospho-ULK1 (Ser638) Antibody recognizes endogenous levels of ULK1 protein only when phosphorylated at Ser638.

Species predicted to react based on 100% sequence homology: Monkey

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Ser638 of human ULK1 protein. Antibodies are purified by protein A and peptide affinity chromatography.

Two related serine/threonine kinases, UNC-51-like kinase 1 and 2 (ULK1, ULK2), were discovered as mammalian homologs of the C. elegans gene UNC-51 in which mutants exhibited abnormal axonal extension and growth (1-4). Both proteins are widely expressed and contain an amino-terminal kinase domain followed by a central proline/serine rich domain and a highly conserved carboxy-terminal domain. The roles of ULK1 and ULK2 in axon growth have been linked to studies showing that the kinases are localized to neuronal growth cones and are involved in endocytosis of critical growth factors, such as NGF (5). Yeast two-hybrid studies found ULK1/2 associated with modulators of the endocytic pathway, SynGAP and syntenin (6). Structural similarity of ULK1/2 has also been recognized with the yeast autophagy protein Atg1/Apg1 (7). Knockdown experiments using siRNA demonstrated that ULK1 is essential for autophagy (8), a catabolic process for the degradation of bulk cytoplasmic contents (9,10). It appears that Atg1/ULK1 can act as a convergence point for multiple signals that control autophagy (11), and can bind to several autophagy-related (Atg) proteins, regulating phosphorylation states and protein trafficking (12-16).

Phosphorylation of ULK1 at Ser638 and Ser757 is mediated by mTOR, which is a regulator of cell growth and an inhibitor of autophagy that disrupts the interaction between ULK1 and AMPK (17,18). Conversely, AMPK is activated during low nutrient conditions and directly phosphorylates ULK1 at multiple sites including Ser317, Ser555, and Ser777 (17-19).

1.  Ogura, K. et al. (1994) Genes Dev 8, 2389-400.

2.  Reggiori, F. and Klionsky, D.J. (2002) Eukaryot Cell 1, 11-21.

3.  Kuroyanagi, H. et al. (1998) Genomics 51, 76-85.

4.  Codogno, P. and Meijer, A.J. (2005) Cell Death Differ 12 Suppl 2, 1509-18.

5.  Yan, J. et al. (1998) Biochem Biophys Res Commun 246, 222-7.

6.  Yan, J. et al. (1999) Oncogene 18, 5850-9.

7.  Zhou, X. et al. (2007) Proc Natl Acad Sci USA 104, 5842-7.

8.  Tomoda, T. et al. (2004) Genes Dev 18, 541-58.

9.  Matsuura, A. et al. (1997) Gene 192, 245-50.

10.  Chan, E.Y. et al. (2007) J Biol Chem 282, 25464-74.

11.  Stephan, J.S. and Herman, P.K. (2006) Autophagy 2, 146-8.

12.  Okazaki, N. et al. (2000) Brain Res Mol Brain Res 85, 1-12.

13.  Young, A.R. et al. (2006) J Cell Sci 119, 3888-900.

14.  Kamada, Y. et al. (2000) J Cell Biol 150, 1507-13.

15.  Lee, S.B. et al. (2007) EMBO Rep 8, 360-5.

16.  Hara, T. et al. (2008) J Cell Biol 181, 497-510.

17.  Shang, L. et al. (2011) Proc Natl Acad Sci U S A 108, 4788-93.

18.  Kim, J. et al. (2011) Nat Cell Biol 13, 132-41.

19.  Egan, D.F. et al. (2011) Science 331, 456-61.

Entrez-Gene Id 8408
Swiss-Prot Acc. O75385

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Phospho-ULK1 (Ser638) Antibody