Phospho-ULK1 (Ser317) Antibody

• 产品编号：CST-6887S      品牌：Cell Signaling Technology       原厂货号：6887S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-ULK1 (Ser317) Antibody 能够检测转染的的Ser317发生磷酸化的ULK1蛋白。该单克隆抗体通过合成肽免疫动物制备，这种合成肽的序列与人源ULK1蛋白Ser317周围残基相一致。UNC-51样激酶1和2(ULK1, ULK2)，是两种相关丝氨酸/苏氨酸激酶，研究发现是秀丽隐杆线虫基因UNC-51的哺乳动物同源物，它的突变会导致轴突的异常延伸与生长(1-4)。两种蛋白广泛表达，并且在一个中央脯氨酸/丝氨酸富含区域，和一个高度保守的羧基末端区域的后面含有一个氨基末端激酶域。关于ULK1和ULK2在轴突生长中的作用，有关研究表明，这些激酶主要定位于神经生长锥中，并且参与临界生长因子的内吞作用，如NGF(5)。酵母双杂交试验研究发现，ULK1/2与内吞作用途径的调节器有关，如SynGAP 和 syntenin(6)。ULK1/2与酵母自噬蛋白Agt1/Apg1具有结构相似性(7)。使用siRNA的敲除实验证明了，ULK1对自噬是必不可少的，即自噬溶酶体对其包裹的细胞质内容物进行降解的一种分解代谢过程(8)。Atg1/ULK1能够作为控制通路的多重信号的聚焦点(11)，并且能够与多种调节磷酸化状态和蛋白运输的自噬相关蛋白(Atg)相结合(12-16)。AMPK，在低营养条件下的活化，可以直接磷酸化ULK1的多个位点，如Ser317、Ser555 和 Ser777 (17,18)。相反，mTOR，能够调节细胞生长和自噬抑制物，可以磷酸化ULK1的Ser757位点，并破坏ULK1和AMPK的相互作用(17)。

1. Ogura, K. et al. (1994) Genes Dev 8, 2389-400.
2. Kuroyanagi, H. et al. (1998) Genomics 51, 76-85.
3. Yan, J. et al. (1998) Biochem Biophys Res Commun 246, 222-7.
4. Yan, J. et al. (1999) Oncogene 18, 5850-9.
5. Zhou, X. et al. (2007) Proc Natl Acad Sci USA 104, 5842-7.
6. Tomoda, T. et al. (2004) Genes Dev 18, 541-58.
7. Matsuura, A. et al. (1997) Gene 192, 245-50.
8. Chan, E.Y. et al. (2007) J Biol Chem 282, 25464-74.
9. Reggiori, F. and Klionsky, D.J. (2002) Eukaryot Cell 1, 11-21.
10. Codogno, P. and Meijer, A.J. (2005) Cell Death Differ 12 Suppl 2, 1509-18.
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. Kim, J. et al. (2011) Nat Cell Biol 13, 132-41.
18. Egan, D.F. et al. (2011) Science 331, 456-61.

原厂资料：

Homology

Species predicted to react based on 100% sequence homology: Human, Rat, Monkey, Bovine

Specificity / Sensitivity

Phospho-ULK1 (Ser317) Antibody recognizes transfected levels of ULK1 protein only when phosphorylated at Ser317.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Ser317 of human ULK1 protein.

Background

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

1. Ogura, K. et al. (1994) Genes Dev 8, 2389-400.
2. Kuroyanagi, H. et al. (1998) Genomics 51, 76-85.
3. Yan, J. et al. (1998) Biochem Biophys Res Commun 246, 222-7.
4. Yan, J. et al. (1999) Oncogene 18, 5850-9.
5. Zhou, X. et al. (2007) Proc Natl Acad Sci USA 104, 5842-7.
6. Tomoda, T. et al. (2004) Genes Dev 18, 541-58.
7. Matsuura, A. et al. (1997) Gene 192, 245-50.
8. Chan, E.Y. et al. (2007) J Biol Chem 282, 25464-74.
9. Reggiori, F. and Klionsky, D.J. (2002) Eukaryot Cell 1, 11-21.
10. Codogno, P. and Meijer, A.J. (2005) Cell Death Differ 12 Suppl 2, 1509-18.
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. Kim, J. et al. (2011) Nat Cell Biol 13, 132-41.
18. Egan, D.F. et al. (2011) Science 331, 456-61.

注意事项：

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.