Phospho-LATS1 (Ser909) Antibody

The Large tumor suppressor (LATS) proteins (LATS1, LATS2) are serine/threonine kinases that belong to the NDR family (1). The Drosophila homolog (warts) was first identified as a tumor suppressor protein that plays a role in the maintenance of ploidy. Human LATS1 was shown to localize to the centrosome and the mitotic spindle and control G2/M transition by negatively regulating cdc2 kinase activity (2,3). LATS1 is also reported to play 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 of LATS1 is associated with breast tumor aggressiveness (7), and mutations perturbing LATS1 have been associated with human sarcomas and ovarian sarcomas (8,9). LATS1 knockout mice develop soft-tissue sarcomas, ovarian stromal cell tumor, and display a high sensitivity to carcinogenic treatments (10). LATS1 and LATS2 have also been identified as key members of the Hippo signaling pathway, a conserved kinase cascade that functions to regulate cell growth and apoptosis (11). Phosphorylation of LATS by Mammalian Sterile-20-like proteins (e.g., MST1) results in LATS-mediated phosphorylation of the transcriptional co-activators YAP and TAZ (12, 13). LATS-mediated phosphorylation of YAP and TAZ promotes their cytoplasmic sequestration and association with 14-3-3 proteins, and subsequent proteasomal degradation, leading to downregulation of YAP/TAZ target genes that promote cell growth (11, 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.