ライフサイエンスコーパス: LATS

1 LATS deficiency in mouse podocytes induced a phenotypic

2 LATS is required for p53 accumulation following failed c

3 LATS kinases phosphorylate and thereby inactivate YAP, t

4 Saccharomyces cerevisiae Cbk1 is a LATS/Ndr protein kinase and a downstream component of th

5 Saccharomyces cerevisiae Cbk1 kinase is a LATS/NDR tumor suppressor orthologue and component of th

6 ith a JNK-dependent increase in binding of a LATS inhibitor, LIMD1, to the LATS1 kinase and that redu

7 90A is obligatory for E-cadherin to activate LATS kinases and induce CIP.

8 Notably, STK25 activates LATS by promoting LATS activation loop phosphorylation i

9 n alpha3 in TA cells that signals through an LATS-independent FAK/CDC42/PP1A cascade to control YAP-S

10 extent with WW45, KIBRA, and Angiomotin, and LATS co-migrated exclusively with USP9X during gel filtr

11 chanism independent of the kinases Hippo and LATS via which YAP is controlled by the innate immune pa

12 plained by the interaction of LIM-kinase and LATS.

13 tion between the key Hippo proteins MOB1 and LATS and stimulating the YAP-mediated genetic program go

14 he core of the pathway consists of a MST and LATS family kinase cascade that ultimately phosphorylate

15 , although serving as an adaptor for MST and LATS, Salvador can also bind RASSF1A.

16 together, the phosphorylation of Amot130 by LATS is found to be a key feature that enables it to inh

17 n response to osmotic stress, as measured by LATS and YAP phosphorylation.

18 a substrate for the Saccharomyces cerevisiae LATS/NDR orthologue Cbk1, which controls polarized growt

19 The core LATS kinases of the Hippo tumor suppressor pathway phosp

20 atures, which are concomitant with decreased LATS and YAP phosphorylation, but not MST1/2.

21 Deleting LATS kinases or expressing YAP variants that evade LATS-

22 its LATS kinase by promoting HSP90-dependent LATS interaction with and inactivation by protein phosph

23 significantly downregulated and destabilized LATS and resulted in enhanced nuclear translocation of Y

24 that can promote YAP1 activity by disrupting LATS-YAP1 phosphorylation.

25 inases or expressing YAP variants that evade LATS-mediated inhibitory phosphorylation induces prolife

26 ggest benchmarks and pathways, such as Hippo-LATS-YAP/TAZ signaling, enriched in these cells.

27 y repressing large tumor suppressor homolog (LATS), and we identify the GTPase-activating protein GIT

28 P binding to the Warts and Salvador homologs LATS and WW45.

29 f budding in Hydra and is regulated by Hydra LATS.

30 Heat shock also induces LATS ubiquitination and degradation.

31 accumulated zinc directly binds and inhibits LATS.

32 Heat shock inhibits LATS kinase by promoting HSP90-dependent LATS interactio

33 n this study, we introduced human LATS1 into LATS(-/-) MEF cells by adenovirus-mediated gene transfer

34 Mechanistically, the Hippo pathway kinase LATS phosphorylates and inhibits MTF1, an essential tran

35 ed and inhibited by the Hippo pathway kinase LATS.

36 -repression between the Hippo pathway kinase LATS/Warts (Wts) and growth regulator Melted generates m

37 The kinase LATS/WARTS is a tumor suppressor protein conserved in ev

38 attenuates phosphorylation of the HP kinase (LATS).

39 activation of large tumor suppressor kinase (LATS), an HP kinase.

40 ile 20-like serine-threonine protein kinase)-LATS (large tumor suppressor serine-threonine protein ki

41 tion of the large tumour suppressor kinases (LATS) 1 and 2, which are part of the Hippo pathway, prom

42 Z inhibitory large tumor suppressor kinases (LATSs).

43 tly, the Amot130 (S175A) mutant, which lacks LATS phosphorylation, bound AIP4 poorly under all condit

44 ippo pathway fine-tunes mechanotransduction: LATS kinases phosphorylate AMOT, shielding it from degra

45 g E-cadherin, which amplifies p190A-mediated LATS activation and is necessary for CIP.

46 mammalian orthologs, like salvador, merlin, LATS, and YAP1, have been implicated in tumorigenesis.

47 In mice, LATS-deficient podocytes orchestrated a profibrotic and

48 acterization of the selective small-molecule LATS kinase inhibitor NIBR-LTSi.

49 Moreover, LATS activity is inhibited following heavy metal treatme

50 growth and homeostasis through a central MST-LATS kinase cascade.

51 The MST-LATS kinase cascade is central to the Hippo pathway that

52 primarily through the inhibition of the MST/LATS cascade.

53 RASSF1A-p.133Ser failed to activate the MST2/LATS pathway, which is required for YAP/p73-mediated apo

54 1-Mob2, to our knowledge the first of an NDR/LATS kinase-Mob complex.

55 hich is activated by the kinase Cbk1, an Ndr/LATS-related protein that functions in a system related

56 We report that the conserved NDR/LATS kinase Orb6 responds to nutritional cues and regula

57 The Ndr/LATS family kinase Cbk1, functioning in a system similar

58 ivity is differentially regulated by the Ndr/LATS family kinase, Cbk1: phosphorylation suppresses PB/

59 ell proliferation and morphogenesis; the NDR/LATS family protein kinases, which associate with "Mob"

60 tion-specific exocytosis function of the NDR/LATS kinase Cbk1, a key component of "hippo" signaling t

61 activation region that may be unique to NDR/LATS kinases, in which a key regulatory motif apparently

62 ynthase kinase 3 but not casein kinase 1 nor LATS in YAP-mediated TAZ loss.

63 rosine residue, which is critical for normal LATS function in vivo.

64 Absence of LATS stabilized ERalpha and the Hippo effectors YAP and

65 of proliferation (CIP) through activation of LATS kinases and phosphorylation of the proto-oncogenic

66 ion distinct from other kinase activators of LATS.

67 Postnatal deletion of LATS kinases and subsequent upregulation of YAP/TAZ lead

68 ts resulted in significant downregulation of LATS.

69 cal (that is, YAP/TAZ-independent) effect of LATS in the regulation of human breast cell fate.

70 athway by influencing the phosphorylation of LATS and YAP, but functional consequences of these bioch

71 We set out to investigate the potential of LATS inhibition as a therapeutic approach to enhance tis

72 In the presence of LATS, ERalpha was targeted for ubiquitination and Ddb1-c

73 the role of SUMOylation in the regulation of LATS activation.

74 kinases in MST1/2-independent regulation of LATS and YAP.

75 ns two WW domains and binds to the Warts (or LATS) protein kinase.

76 Finally, we show that dCSK phosphorylates LATS in vitro at a conserved C-terminal tyrosine residue

77 We developed a potent LATS inhibitor VT02956.

78 lts strongly indicate that USP9X potentiates LATS kinase to suppress tumor growth.

79 overexpression in murine podocytes promoted LATS kinase phosphorylation, leading to subsequent YAP S

80 Notably, STK25 activates LATS by promoting LATS activation loop phosphorylation independent of a pr

81 -threonine kinase, a component of the RASSF1-LATS tumor suppressor network, is involved in cell proli

82 ritical role of PITPalpha/beta in regulating LATS and YAP.

83 Together, we report a selective LATS kinase inhibitor agonizing YAP signaling and promot

84 1 may limit tumor progression by stabilizing LATS and thereby promoting activity of the Hippo tumor s

85 e previously shown the activation of the STK/LATS/YAP/TAZ signalling cascade in the developing and po

86 Our study suggests LATS as unexpected cancer therapeutic targets, especiall

87 pancreatic tumors, with the tumor suppressor LATS exhibiting enhanced ubiquitin-dependent proteasomal

88 ed upon silencing of large tumor suppressor (LATS)-1 and LATS2, direct substrates of Mst2.

89 Large tumor suppressor (LATS)1/2 protein kinases transmit Hippo signaling in res

90 Large tumour suppressor (LATS) 1/2, the core kinases of Hippo signalling, are cri

91 f the Hippo kinases large tumor suppressors (LATS)1 and 2, which serve to inactivate the transcriptio

92 n multiple organs prevent prolonged systemic LATS inhibition, thus limiting potential therapeutic ben

93 inhibition of the Hippo pathway by targeting LATS kinases is sufficient to drive ectopic TE initiatio

94 Furthermore, we find that LATS can synergize with F-actin perturbations by phospho

95 These biochemical observations indicate that LATS is a novel negative regulator of CDC2/cyclin A, a f

96 Here, we show that LATS proteins (mammalian orthologs of Warts) interact di

97 The LATS family of serine/threonine kinases control tissue s

98 The LATS tumor suppressor kinases phosphorylate and inhibit

99 d show that HSP90 inhibitors can disrupt the LATS tumor suppressor pathway in human cancer cells.

100 Our findings identify the LATS/YAP/TAZ signalling cascade as an essential componen

101 f LATS1 and decreased phosphorylation of the LATS substrate YAP, an oncoprotein transcriptional coact

102 Ssd1 is a substrate of the LATS/NDR tumour suppressor orthologue Cbk1 kinase.

103 r adaptor protein couples MST kinases to the LATS kinases to form the hippo pathway.

104 Thus, this LATS-mediated feedback loop provides an efficient mechan

105 nsitive to LATS kinase activity, even though LATS proteins normally do not limit activity of TEAD4, Y

106 tively regulated by Hippo signalling through LATS-mediated phosphorylation and is mediated by the coi

107 f premature Sox2 expression was sensitive to LATS kinase activity, even though LATS proteins normally

108 lso shown that LATS2 kinase activity and two LATS conserved domains (LCDs) are required for Lats2 to

109 uman Ndr; and Drosophila and mammalian WARTS/LATS kinases.

110 ng a cytosolic Hippo kinase complex in which LATS kinase is inhibited.

111 cells, Ajuba LIM proteins/dJub interact with LATS/Warts (Wts) and WW45/Sav to inhibit phosphorylation

112 with MOB1 and enhanced its interaction with LATS, thereby providing a signaling connection between t

113 apen homolog MAP4K4 similarly interacts with LATS (Warts homolog) and promotes inhibition of YAP (Yor

114 rotein expression correlated positively with LATS but negatively with YAP/TAZ in pancreatic cancer ti

115 USP9X interacted strongly with LATS kinase and to a lesser extent with WW45, KIBRA, and