LATS1: an AGC kinase of the NDR family of kinases. Localized to the mitotic apparatus and specifically phosphorylated during mitosis. A likely tumor suppressor which plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G1 tetraploidy checkpoint. Negatively regulates G2/M transition by down-regulating CDC2 kinase activity, causing G2 arrest. Involved in the control of p53 expression. Affects cytokinesis by regulating actin polymerization through negative modulation of LIMK1. Complexes with CDC2 in early mitosis. LATS1-associated CDC2 has no mitotic cyclin partner and no apparent kinase activity. Binds phosphorylated zyxin, locating this protein to the mitotic spindle and suggesting a role for actin regulatory proteins during mitosis. Binds to and colocalizes with LIMK1 at the actomyosin contractile ring during cytokinesis. Knockout mice are susceptible to soft-tissue sarcomas and sensitive to chemical carcinogenesis. Human soft tissue sarcomas have downregulated, mutated, and/or hypermethylated LATS1. Transgenic expression blocks anchorage independent growth in culture and tumor growth in xenografts. Two alternatively spliced isoforms of the human proteinhave been described.
Protein type: Kinase, protein; Tumor suppressor; EC 2.7.11.1; Protein kinase, AGC; Protein kinase, Ser/Thr (non-receptor); AGC group; NDR family
Chromosomal Location of Human Ortholog: 6q25.1
Cellular Component: spindle pole; microtubule organizing center; cytosol
Molecular Function: protein serine/threonine kinase activity; protein binding; magnesium ion binding; protein kinase binding; ATP binding
Biological Process: keratinocyte differentiation; mitosis; regulation of actin filament polymerization; hormone-mediated signaling; cell division; negative regulation of cyclin-dependent protein kinase activity; cytoplasmic sequestering of protein; sister chromatid segregation; regulation of protein complex assembly; G2/M transition of mitotic cell cycle; positive regulation of peptidyl-serine phosphorylation; protein amino acid phosphorylation
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