The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1

  title={The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1},
  author={Eunice H. Y. Chan and Marjaana Nousiainen and Ravindra B. Chalamalasetty and A J Sch{\"a}fer and Erich A. Nigg and Herman H. W. Sillj{\'e}},
Originally identified in Drosophila melanogaster, the Warts(Wts)/Lats protein kinase has been proposed to function with two other Drosophila proteins, Hippo (Hpo) and Salvador (Sav), in the regulation of cell cycle exit and apoptosis. In mammals, two candidate Warts/Lats homologs, termed Lats1 and Lats2, have been described, and the targeted disruption of LATS1 in mice increases tumor formation. Little, however, is known about the function and regulation of human Lats kinases. Here we report… 

Mammalian NDR/LATS protein kinases in hippo tumor suppressor signaling

Current knowledge of Merlin/MST/SAV/MOB/LATS/NDR/YAP/TAZ networks (also termed mammalian Hippo signaling) and their roles in mammalian cellular transformation are summarized.

Itch E3 ubiquitin ligase regulates large tumor suppressor 1 stability

It is revealed that change of Itch abundance alone is sufficient for altering LATS1-mediated downstream signaling, negative regulation of cell proliferation, and induction of apoptosis and presents a possibility of targeting LATS 1/Itch interaction as a therapeutic strategy in cancer.

The human tumour suppressor LATS1 is activated by human MOB1 at the membrane.

Tumor Suppressor LATS1 Is a Negative Regulator of Oncogene YAP*

Significantly, it is discovered that LATS1 inactivates YAP oncogenic function by suppressing its transcription regulation of cellular genes via sequestration of YAP in the cytoplasm after phosphorylation of Y AP.

Downstream of human NDR kinases: Impacting on c-myc and p21 protein stability to control cell cycle progression

The mammalian genome encodes four members of the NDR/LATS kinase family: NDR1, NDR2 (STK38L), LATS1 and LATS2, which are highly conserved from yeast to man andigate on possible explanations for the opposing functions of NDR kinases in normal and tumor biology.

Regulation of Hippo Pathway Kinases MST1/2 by DLG5 and Other Signaling Factors

This work characterized DLG5 as a new and conserved component of the Hippo pathway, a widely conserved, large, multi-domain containing protein, which plays a role in maintenance of epithelial cell polarity.

Phosphorylation of SAV1 by mammalian ste20-like kinase promotes cell death.

Results suggest that MST-mediated phosphorylation of four residues within SAV1 may be important in the induction of cell death by the MST pathway.

Regulation and functions of mammalian LATS/NDR kinases: looking beyond canonical Hippo signalling

Current understanding of mammalian LATS1/2 kinases together with their closest relatives, the NDR1/1 kinases are summarized and the regulation of the LATS/NDR family of kinases will be discussed, followed by a summary of all currently known LATS-NDR substrates.

Biosignaling of mammalian Ste20-related kinases.




Phosphorylation and Dimerization Regulate Nucleocytoplasmic Shuttling of Mammalian STE20-like Kinase (MST)*

Using anti-MST monoclonal antibodies, it is clearly shown that endogenous MST is localized in cytoplasm in a leptomycin B-dependent manner and regulation of localization is important to the biological function of MST, including its effects on cellular morphology.

The centrosomal protein Lats2 is a phosphorylation target of Aurora‐A kinase

It is concluded that S83 of Lats2 is a phosphorylated target of Aurora‐A and this phosphorylation plays a role of the centrosomal localization of Lets2.

Lats2, a putative tumor suppressor, inhibits G1/S transition

A model in which a combination of mammalian Lats2 and Lats1 control cell proliferation by negatively regulating different cell cycle check points is proposed.

Ndr Protein Kinase Is Regulated by Phosphorylation on Two Conserved Sequence Motifs*

It is shown here that Ndr is potently activated when intact cells are treated with okadaic acid, suggesting that NDr is normally held in a state of low activity by protein phosphatase 2A.

Human homologue of Drosophila lats, LATS1, negatively regulate growth by inducing G2/M arrest or apoptosis

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Molecular cloning of a novel human protein kinase, kpm, that is homologous to warts/lats, a Drosophila tumor suppressor

The results suggest that kpm plays a role in cell cycle progression during mitosis and its deletion or dysfunction might be involved in certain types of human cancers.

Structure, expression, and chromosome mapping of LATS2, a mammalian homologue of the Drosophila tumor suppressor gene lats/warts.

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MST, a Physiological Caspase Substrate, Highly Sensitizes Apoptosis Both Upstream and Downstream of Caspase Activation*

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Newly identified stress-responsive protein kinases, Krs-1 and Krs-2.

Two protein kinases are described that are activated by a subset of stress conditions or apoptotic agents but are not activated by commonly used mitogenic stimuli.