Phospho-LATS1 (Thr1079) (D57D3) Rabbit mAb

• 产品编号：CST-8654S      品牌：CST       原厂货号：8654S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-LATS1 (Thr1079) (D57D3) Rabbit mAb能够识别内源性苏氨酸（1079位）磷酸化的LATS1蛋白。该抗体预计与苏氨酸（1041位）磷酸化的LATS2蛋白有交叉反应。该单克隆抗体是由合成的人源的针对LATS1蛋白苏氨酸（1079位）的磷酸化肽段免疫动物生产的。LATS1（大的肿瘤抑制基因1）是一个假定的丝氨酸/苏氨酸激酶，属于NDR家族（1）。肿瘤抑制基因在染色体倍性维持中发挥着关键的作用。LATS1集中分布于中心体和有丝分裂纺锤体，它通过负调控cdc2激酶活性来控制G2/M期转换(2,3)。它也可以通过控制p53的表达在G1期四倍体检验点中发挥作用(4)。LATS1通过负调节LIMK1来调控肌动蛋白聚合从而影响细胞质分裂(5)。LATS1也可以结合磷酸化形式的斑联蛋白，一种肌动蛋白丝组装的调节子。这种相互作用可以促进斑联蛋白向有丝分裂的纺锤体转移，表明了其在有丝分裂过程中调节肌动蛋白的作用(6)。LATS1表达下调和乳腺癌侵袭 (7)、启动子甲基化以及杂合性缺失有关。人类肉瘤和卵巢肉瘤也与突变引起的LATS1变化有关(8,9)。LATS1敲除的小鼠能够发生软组织肉瘤、卵巢间质细胞瘤和致癌处理的高敏感性(10)。最近发现人LATS1以复合体的形式存在，该复合体类似于Drosophila Hippo/Salvador/Lats肿瘤抑制基因网络，它通过调节细胞增殖和凋亡来控制果蝇的生长和形状。相应的人类的复合体包括Hipp和Salvador同源蛋白。RASSF1A, WW45和MST2可以控制有丝分裂退出(11)。Hippo通路的许多参与分子已经被发现，但是目前对于控制这些蛋白激活的机制及控制通路激活的机制仍然不明了。与Mob1联合的同时，LATS1和LATS2被磷酸化，而Mob1由Mst1/2 磷酸化(12,13) 。YAP的激活需要LATS1和LATS2的磷酸化，YAP是Hippo信号通路的一个重要调节子(14)。

1. Tao, W. et al. (1999) Nat Genet 21, 177-81.
2. Yang, X. et al. (2001) Oncogene 20, 6516-23.
3. Xia, H. et al. (2002) Oncogene 21, 1233-41.
4. Iida, S. et al. (2004) Oncogene 23, 5266-74.
5. Yang, X. et al. (2004) Nat Cell Biol 6, 609-17.
6. Hirota, T. et al. (2000) J Cell Biol 149, 1073-86.
7. Morinaga, N. et al. (2000) Int J Oncol 17, 1125-9.
8. Hansen, L.L. et al. (2002) Cancer Genet Cytogenet 139, 1-8.
9. Hisaoka, M. et al. (2002) Lab Invest 82, 1427-35.
10. St John, M.A. et al. (1999) Nat Genet 21, 182-6.
11. Guo, C. et al. (2007) Curr Biol 17, 700-5.
12. Hergovich, A. et al. (2006) Biochem Biophys Res Commun 345, 50-8.
13. Hirabayashi, S. et al. (2008) Oncogene 27, 4281-92.
14. Zhao, B. et al. (2010) J Cell Sci 123, 4001-6.

原厂资料：

Homology

Species predicted to react based on 100% sequence homology: Rat, Monkey, Chicken, Xenopus, Zebrafish, Dog

Specificity / Sensitivity

Phospho-LATS1 (Thr1079) (D57D3) Rabbit mAb detects endogenous levels of LATS1 protein only when phosphorylated at Thr1079. This antibody is predicted to cross react with LATS2 only when LATS2 is phosphorylated at Thr1041. 

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Thr1079 of human LATS1 protein. 

Background

LATS1 (Large tumor suppressor 1) is a putative serine/threonine kinase that belongs to the NDR family (1). It is a tumor suppressor that plays a critical role in the maintenance of ploidy. LATS1 localizes to the centrosome and the mitotic spindle and controls G2/M transition by negatively regulating cdc2 kinase activity (2,3). LATS1 also plays a role in the G1 tetraploidy checkpoint via control of p53 expression (4). 
 LATS1 affects cytokinesis by regulating actin polymerization through negative modulation of LIMK1 (5). LATS1 also binds the phosphorylated form of zyxin, a regulator of actin filament assembly. This interaction promotes localization of zyxin to the mitotic spindle, suggesting a role for actin regulatory proteins during mitosis (6). Decreased expression is associated with breast tumor aggressiveness (7), promoter methylation, and loss of heterozygosity. Mutations perturbing LATS1 have been associated with human sarcomas and ovarian sarcomas (8,9). LATS1 knock out mice develop soft-tissue sarcomas, ovarian stromal cell tumor, and display a high sensitivity to carcinogenic treatments (10). 
 Human LATS1 exists in a complex similar to the Drosophila Hippo/Salvador/Lats tumor suppressor network, a complex that regulates proliferation and apoptosis to control growth and shape of the fly. The corresponding human complex contains Hippo and Salvador homologs RASSF1A, WW45, and MST2 and may control mitotic exit (11). 
 
 Many molecules have been discovered that are involved in the Hippo pathway, but mechanisms governing activation of these proteins and activation of the pathway in general are currently not clear. Phosphorylation of LATS1 and LATS2 is stimulated by association with Mob1, which is itself phosphorylated by Mst1/2 (12,13). Phosphorylation of LATS1/2 is required for activation of YAP, a key mediator of the Hippo signaling pathway (14). 

1. Tao, W. et al. (1999) Nat Genet 21, 177-81.
2. Yang, X. et al. (2001) Oncogene 20, 6516-23.
3. Xia, H. et al. (2002) Oncogene 21, 1233-41.
4. Iida, S. et al. (2004) Oncogene 23, 5266-74.
5. Yang, X. et al. (2004) Nat Cell Biol 6, 609-17.
6. Hirota, T. et al. (2000) J Cell Biol 149, 1073-86.
7. Morinaga, N. et al. (2000) Int J Oncol 17, 1125-9.
8. Hansen, L.L. et al. (2002) Cancer Genet Cytogenet 139, 1-8.
9. Hisaoka, M. et al. (2002) Lab Invest 82, 1427-35.
10. St John, M.A. et al. (1999) Nat Genet 21, 182-6.
11. Guo, C. et al. (2007) Curr Biol 17, 700-5.
12. Hergovich, A. et al. (2006) Biochem Biophys Res Commun 345, 50-8.
13. Hirabayashi, S. et al. (2008) Oncogene 27, 4281-92.
14. Zhao, B. et al. (2010) J Cell Sci 123, 4001-6.

注意事项：

Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150
mM NaCl, 100 µg/ml BSA, 50% glycerol and less than 0.02%
sodium azide. Store at –20°C. Do not aliquot the antibody.