ライフサイエンスコーパス: lipin

1 the mammalian phospatidic acid phosphatase, lipin.

2 ines and arginines of the PBD vary among the lipins.

3 In fat pads from mice deficient for lipin 1 (fld mice) and in 3T3-L1 adipocytes depleted of

4 However, livers of 8-day-old mice lacking lipin 1 (fld mice) exhibited normal PAP-1 activity and a

5 membranes, the effects of phosphorylation on lipin 1 activity and binding to membranes has not been r

6 ts their activity and lipid binding and that lipin 1 activity is negatively regulated by phosphorylat

7 In this work, we characterized human lipin 1 alpha, beta, and gamma isoforms that were expres

8 ribe here the functional interaction between lipin 1 and the nuclear factor of activated T cells c4 (

9 ared by the mammalian fat-regulating protein lipin 1 and the superfamily of haloacid dehalogenase-lik

10 portant roles in the membrane association of lipin 1 and thus the regulation of its enzymatic activit

11 These findings establish lipin 1 as a key component of the mTORC1-SREBP pathway.

12 These observations place lipin 1 as a potentially important link between triacylg

13 Taken together, our findings identify lipin 1 as a reciprocal regulator of triglyceride synthe

14 This depends on our observation that lipin 1 binding to PA in membranes is highly responsive

15 ssed in adipocytes, and constitutive loss of lipin 1 blocks adipocyte differentiation; however, the e

16 Catalytically active and inactive lipin 1 can suppress NFATc4 transcriptional activity, an

17 2 protein content was markedly increased by lipin 1 deficiency, food deprivation, and obesity, often

18 The lipin 1 enzyme with the lipin 3 PBD lost its ability to

19 lar mechanisms involved in the regulation of lipin 1 expression by physiologic stimuli.

20 Consistent with these findings, lipin 1 expression was significantly related to adipose

21 ssion of PGC-1alpha in HepG2 cells increased lipin 1 expression.

22 MitoPLD and Lipin 1 have opposing effects on mitochondria length and

23 essential for the fat-regulating function of lipin 1 in a mouse model.

24 s was due to the lack of the PAP activity of lipin 1 in adipocytes after day 4 of differentiation, wh

25 Loss of lipin 1 in mice inhibits adipogenesis at an early stage

26 Loss of lipin 1 in the mouse, but not in humans, leads to lipody

27 Lipin 1 is a bifunctional intracellular protein that reg

28 Lipin 1 is a bifunctional protein that regulates gene tr

29 Lipin 1 is a coregulator of DNA-bound transcription fact

30 have demonstrated that highly phosphorylated lipin 1 is enriched in the cytosol and dephosphorylated

31 enriched in the cytosol and dephosphorylated lipin 1 is found on membranes, the effects of phosphoryl

32 Lipin 1 is highly expressed in adipocytes, and constitut

33 and suggest that regulation of lipolysis by lipin 1 is mediated by PA-dependent modulation of phosph

34 ity through protein-protein interaction, and lipin 1 is present at the promoters of NFATc4 transcript

35 We sought to determine the expression of lipin 1 isoforms (lipin 1alpha and -beta) in liver and a

36 ion of the deficient mice also revealed that lipin 1 normally modulates cAMP-dependent signaling thro

37 Conversely, the presence of the lipin 1 PBD in lipin 3 subjected the enzyme to negative

38 teasomal degradation was conserved for human lipin 1 phosphatidate phosphatase.

39 cial upstream signaling component regulating lipin 1 phosphorylation.

40 Lipin 1 plays critical roles in controlling energy metab

41 hosphorylated, nuclear, catalytically active lipin 1 promotes nuclear remodeling and mediates the eff

42 Finally, both lipin 1 protein and total PAP activity are decreased wit

43 ctedly resulted in expression of a truncated lipin 1 protein lacking PAP activity but retaining trans

44 Lipin 1 represses NFATc4 transcriptional activity throug

45 To do so, we generated lipin 1 that contained the PBD of lipin 3 and vice versa

46 d mice) and in 3T3-L1 adipocytes depleted of lipin 1 there is increased expression of several NFAT ta

47 lates the ability of the polybasic domain of lipin 1 to recognize di-anionic PA and identify mTOR as

48 e results demonstrate how phosphorylation of lipin 1 together with pH and membrane phospholipid compo

49 rein we describe a new biochemical assay for lipin 1 using mixtures of phosphatidic acid (PA) and pho

50 Second, the expression of lipin 1 was evaluated in HepG2 cells in response to over

51 The movement of lipin 1 within the cell is closely associated with its p

52 es SREBP by controlling the nuclear entry of lipin 1, a phosphatidic acid phosphatase.

53 We found that depletion of lipin 1, after the initiation of differentiation in 3T3-

54 ng triglyceride synthesis, including AGPAT2, lipin 1, and DGAT2, was persistently reduced and lipid a

55 We provide evidence that lipin 2, like lipin 1, binds PA via the electrostatic hydrogen bond sw

56 Like lipin 1, lipin 2 is highly phosphorylated, and we identi

57 In lipin 1, the PBD is the site of PA binding and sensing o

58 However, unlike lipin 1, the phosphorylation of lipin 2 is not induced b

59 This PA in turn recruits the phosphatase Lipin 1, which converts PA to diacylglycerol and promote

60 The human LPIN1 gene encodes the protein lipin 1, which possesses phosphatidate (PA) phosphatase

61 REBP function and makes mice resistant, in a lipin 1-dependent fashion, to the hepatic steatosis and

62 Loss of lipin 1-mediated PAP activity in adipocytes led to reduc

63 ee of phosphorylation-mediated regulation of lipin 1.

64 previously investigated the biochemistry of lipins 1 and 2 and shown that di-anionic phosphatidic ac

65 down-regulated by the combined depletion of lipins 1 and 2 at day 4 of differentiation.

66 We show that the different PBDs of lipins 1 and 3 are responsible for the presence of phosp

67 Lipins 1, 2, and 3 are Mg(2+)-dependent phosphatidic aci

68 Mammals express three paralogues: lipins 1, 2, and 3.

69 pin family of PA phosphatases is composed of lipins 1-3, which are members of the conserved haloacid

70 Lipin-1 also functions as a transcriptional coactivator

71 tions of other residues in the N terminus of lipin-1 also modulate PP-1cgamma binding.

72 trate that myeloid cell-specific deletion of lipin-1 ameliorated inflammation and alcoholic hepatitis

73 a binds poorly to a phosphomimetic mutant of lipin-1 and binds well to the non-phosphorylatable lipin

74 Lipin-1 and lipin-2 are required for normal lipid homeos

75 Combined lipin-1 and lipin-2 deficiency caused embryonic lethalit

76 uncovered a functional relationship between lipin-1 and lipin-2 that operates in a tissue-specific a

77 t mutation of the equivalent serine in mouse lipin-1 and lipin-2 to leucine or aspartate abolishes PA

78 We also demonstrated for the first time that lipin-1 and PAP2a contribute to macrophage inflammation

79 ivated receptor-response elements similar to lipin-1 and that this activity is not affected by mutati

80 ndings demonstrate an unanticipated role for lipin-1 as a mediator of macrophage proinflammatory acti

81 We found that lipin-1 binds to PP-1cgamma through a similar HVRF bindi

82 nsulin may modulate the cellular function of lipin-1 by regulating its subcellular localization throu

83 nts designed to increase SIRT1 regulation of lipin-1 can be developed to treat patients with alcoholi

84 Lipin-1 catalyzes the formation of diacylglycerol from p

85 Disruption of the Lpin1 gene encoding lipin-1 causes impaired adipose tissue development and f

86 e nucleus and may therefore be important for lipin-1 co-activator function.

87 ied by lipin-1, lipin-2, or lipin-3, but not lipin-1 coactivator activity, can rescue Pparg gene expr

88 ed impairment of hepatic SIRT1 signaling via lipin-1 contributes to development of alcoholic steatosi

89 The effects of lipin-1 deficiency appear to include both the loss of gl

90 Mechanistically, myeloid cell-specific lipin-1 deficiency concomitantly increased the fat-deriv

91 adiponectin and FGF15, myeloid cell-specific lipin-1 deficiency diminished hepatic nuclear factor kap

92 Liver-specific lipin-1 deficiency in mice exacerbates the development a

93 as has been observed in mice and humans with lipin-1 deficiency, the pathophysiology in lipin-2 defic

94 Furthermore, lipin-1 expression levels in adipose tissue and/or liver

95 In the present study, we assessed lipin-1 function in myeloid cells in ALD using a myeloid

96 Lipin-1 functions as a phosphatidate phosphatase (PAP) e

97 conclusion, ethanol-induced up-regulation of lipin-1 gene expression is mediated through inhibition o

98 es showed that ethanol-mediated induction of lipin-1 gene expression was inhibited by a known activat

99 nvolved in ethanol-mediated up-regulation of lipin-1 gene expression.

100 de to suppress ethanol-mediated induction of lipin-1 gene-expression level.

101 SRE-containing region in the promoter of the lipin-1 gene.

102 motif in the highly conserved N terminus of lipin-1 greatly decreases PP-1cgamma interaction.

103 In addition, animals lacking lipin-1 had a faster recovery from endotoxin administrat

104 Lipin-1 has been implicated in the pathogenesis of alcoh

105 3-3 promotes the cytoplasmic localization of lipin-1 in 3T3-L1 adipocytes.

106 Studies of lipin-1 in adipocytes have shed some light on its relati

107 ies further revealed that hepatic removal of lipin-1 in mice augmented ethanol-induced impairment of

108 Surprisingly, deletion of lipin-1 in myeloid cells dramatically attenuated liver i

109 aimed to investigate the functional role of lipin-1 in the development of alcoholic steatohepatitis

110 r lipin-1 nuclear localization, and identify lipin-1 interaction with 14-3-3 as a determinant of its

111 We demonstrate that lipin-1 interacts with 14-3-3 proteins and that overexpr

112 Lipin-1 is a bifunctional protein involved in lipid meta

113 Lipin-1 is a Mg(2+)-dependent phosphatidic acid phosphat

114 Lipin-1 is a phosphatidate phosphatase in glycerolipid b

115 Lipin-1 is a phosphatidate phosphohydrolase (PAP) requir

116 Our results suggest that lipin-1 is a potential target for cancer therapy.

117 Lipin-1 is a protein that exhibits dual functions as a p

118 Lipin-1 is critical for lipid synthesis and homeostasis

119 This indicates that lipin-1 is dephosphorylated before PP-1cgamma binds to i

120 Previous studies established that lipin-1 is required at an early step in adipocyte differ

121 w for the first time, to our knowledge, that lipin-1 knockdown significantly inhibits tumor growth in

122 d cells in ALD using a myeloid cell-specific lipin-1 knockout (mLipin-1KO) mouse model.

123 and an age-dependent reduction in cerebellar lipin-1 levels, resulting in altered cerebellar phosphol

124 logical or nutritional modulation of hepatic lipin-1 may be beneficial for the prevention or treatmen

125 1 and binds well to the non-phosphorylatable lipin-1 mutant.

126 Lipin-1 mutations cause lipodystrophy in mice and acute

127 vide novel evidence of the importance of the lipin-1 N-terminal domain for its catalytic activity, nu

128 alization signal alone is not sufficient for lipin-1 nuclear localization, and identify lipin-1 inter

129 studies have identified mutations that cause lipin-1 or lipin-2 deficiency in humans, leading to acut

130 and this can be rescued by the expression of lipin-1 PAP activity or by inhibition of ERK signaling.

131 Here, we investigate the requirement of lipin-1 PAP versus coactivator function in the establish

132 on of 3T3-L1 adipocytes results in increased lipin-1 phosphorylation, enhanced interaction with 14-3-

133 Lipin-1 plays a role in the biosynthesis of triacylglyce

134 xposure robustly induced activity of a mouse lipin-1 promoter, promoted cytoplasmic localization of l

135 cy led to a compensatory increase in hepatic lipin-1 protein and elevated PAP activity, which maintai

136 Lipin-1 regulates lipid metabolism by way of its functio

137 Lipin-1 regulation of phospholipid synthesis maintains e

138 Hyperphosphorylated lipin-1 remains sequestered in the cytosol, whereas hypo

139 Lipin-1 resides in the cytoplasm and translocates to the

140 ure, largely by reversing the aberrations in lipin-1 signaling induced by ethanol.

141 d in the cytosol, whereas hypophosphorylated lipin-1 translocates to the endoplasmic reticulum and nu

142 The effects of ethanol on lipin-1 were investigated in cultured hepatic cells and

143 inal kinase activation and downregulation of lipin-1, a novel PXR target gene.

144 We found that LPIN1, which encodes lipin-1, a phosphatidic acid phosphatase (PAP) controlli

145 tabolism, mainly by altering the function of lipin-1, a transcriptional regulator of lipid metabolism

146 re importantly, miR-217 impairs functions of lipin-1, a vital lipid regulator, in hepatocytes.

147 in liver, where levels were much higher than lipin-1, and also in kidney, lung, gastrointestinal trac

148 omoter, promoted cytoplasmic localization of lipin-1, and caused excess lipid accumulation, both in c

149 of nematode CTDNEP1 and NEP1-R1, as well as lipin-1, is required for normal nuclear membrane breakdo

150 The genes for lipin-1, lipin-2 and lipin-3 are expressed in key metabo

151 Mammalian lipins (lipin-1, lipin-2, and lipin-3) are Mg2+-dependent phosph

152 We demonstrate that PAP activity supplied by lipin-1, lipin-2, or lipin-3, but not lipin-1 coactivato

153 In the present study, using a liver-specific lipin-1-deficient (lipin-1LKO) mouse model, we aimed to

154 Using macrophages from lipin-1-deficient animals and human macrophages deficien

155 After TLR4 stimulation lipin-1-deficient macrophages showed a decreased product

156 In adipose tissue from lipin-1-deficient mice, there is an accumulation of phos

157 ssion and lipogenesis during adipogenesis in lipin-1-deficient preadipocytes.

158 an and mouse tissues closely mirrors that of lipin-1.

159 is mediated through a serine-rich domain in lipin-1.

160 on and phosphatidate phosphatase activity of lipin-1.

161 CTDNEP1 can dephosphorylate lipins-1a, -1b, and -2 in human cells only in the presen

162 The expression of lipin 1alpha and -beta was quantified in liver and adipo

163 etermine the expression of lipin 1 isoforms (lipin 1alpha and -beta) in liver and adipose tissue of o

164 levels of SIRT1, SFRS10, and lipin-1beta and lipin-1alpha in liver samples from patients with alcohol

165 The nuclear fraction of lipin-1b is increased when CTDNEP1 and NEP1-R1 are co-ex

166 the presence of c-Fos, with no change in the lipin 1beta affinity for the PA/Triton X-100 mixed micel

167 These studies suggest that hepatic lipin 1beta and PGC-1alpha expression are downregulated

168 We studied the lipin 1beta enzyme activity in a cell-free system using

169 The expression of lipin 1beta in liver and adipose tissue was inversely re

170 We found that lipin 1beta kcat value increases around 40% in the prese

171 Hepatic lipin 1beta mRNA levels were strongly correlated with th

172 Finally, overexpression of lipin 1beta or PGC-1alpha reversed the effect of hyperin

173 e evidence for a novel positive regulator of lipin 1beta PA phosphatase activity that is not achieved

174 e conditions downregulated the expression of lipin 1beta, PGC-1alpha, and their known target genes in

175 d messenger RNA levels of SIRT1, SFRS10, and lipin-1beta and lipin-1alpha in liver samples from patie

176 Surprisingly, chronically ethanol-fed lipin-1LKO mice showed markedly greater hepatic triglyce

177 y was achieved by pair feeding wild-type and lipin-1LKO mice with modified Lieber-DeCarli ethanol-con

178 y, using a liver-specific lipin-1-deficient (lipin-1LKO) mouse model, we aimed to investigate the fun

179 Importantly, phosphorylation of lipin 2 does not negatively regulate either membrane bin

180 This suggests that lipin 2 functions as a constitutively active PA phosphat

181 Lipin 2 is a phosphatidic acid phosphatase (PAP) respons

182 Like lipin 1, lipin 2 is highly phosphorylated, and we identified 15 p

183 ever, unlike lipin 1, the phosphorylation of lipin 2 is not induced by insulin signaling nor is it se

184 y 4 of differentiation, whereas depletion of lipin 2 led to an increase of lipid droplet volume per c

185 Importantly, RNAi against lipin 2 markedly reduced PAP-1 activity in hepatocytes f

186 Collectively, these data suggest that lipin 2 plays an important role as a hepatic PAP-1 enzym

187 (lipin 2) is enriched in liver, and hepatic lipin 2 protein content was markedly increased by lipin

188 This knowledge of lipin 2 regulation is important for a deeper understandi

189 Another member of the lipin family (lipin 2) is enriched in liver, and hepatic lipin 2 prote

190 lycerol, results in a reciprocal increase of lipin 2, but not lipin 3.

191 We provide evidence that lipin 2, like lipin 1, binds PA via the electrostatic hy

192 l understanding of the biochemical nature of lipin 2, we have performed kinetic and phosphorylation a

193 To characterize sites of lipin-2 action, we detected lipin-2 expression by in sit

194 Lipin-2 also inhibits the activation and sensitization o

195 The genes for lipin-1, lipin-2 and lipin-3 are expressed in key metabolic tissu

196 Lipin-1 and lipin-2 are required for normal lipid homeostasis and ha

197 Collectively, our results unveil lipin-2 as a critical player in the negative regulation

198 We show here that lipin-2 controls excessive IL-1beta formation in primary

199 cholesterol concentrations in cells lacking lipin-2 decreases ion currents through the P2X7 receptor

200 This was associated with the combination of lipin-2 deficiency and an age-dependent reduction in cer

201 Combined lipin-1 and lipin-2 deficiency caused embryonic lethality.

202 e identified mutations that cause lipin-1 or lipin-2 deficiency in humans, leading to acute myoglobin

203 h lipin-1 deficiency, the pathophysiology in lipin-2 deficiency is associated with dysregulation of l

204 In liver, lipin-2 deficiency led to a compensatory increase in hep

205 However the role of lipin-2 during IL-1beta production remains elusive.

206 cterize sites of lipin-2 action, we detected lipin-2 expression by in situ hybridization on whole mou

207 Mutations in the human lipin-2 gene are associated with inflammatory-based diso

208 We also determined that lipin-2 has transcriptional coactivator activity for per

209 matory-based disorders; however, the role of lipin-2 in cells of the immune system remains obscure.

210 lipin family in vivo, and a unique role for lipin-2 in central nervous system biology that may be pa

211 e data provide new insights into the role of lipin-2 in human and murine macrophage biology and may o

212 Reduced levels of lipin-2 in macrophages lead to a decrease in cellular ch

213 se studies demonstrate a protective role for lipin-2 in proinflammatory signaling mediated by saturat

214 this study, we have investigated the role of lipin-2 in the proinflammatory action of saturated fatty

215 Lipin-2 is a member of the lipin family of enzymes, whic

216 sults raise the possibility that the loss of lipin-2 PAP activity in erythrocytes and lymphocytes may

217 of the Majeed syndrome result from a loss of lipin-2 PAP activity.

218 Depletion of lipin-2 promotes the increased expression of the proinfl

219 Metabolically, the absence of lipin-2 reduces the cellular content of triacylglycerol

220 In contrast, overexpression of lipin-2 reduces the release of proinflammatory factors.

221 Lipin-2 regulates MAPK activation, which mediates synthe

222 functional relationship between lipin-1 and lipin-2 that operates in a tissue-specific and age-depen

223 f the equivalent serine in mouse lipin-1 and lipin-2 to leucine or aspartate abolishes PAP activity b

224 Lipin-2 was also expressed in circulating red blood cell

225 Lipin-2 was most prominently expressed in liver, where l

226 Mammalian lipins (lipin-1, lipin-2, and lipin-3) are Mg2+-dependent phosphatidate p

227 trate that PAP activity supplied by lipin-1, lipin-2, or lipin-3, but not lipin-1 coactivator activit

228 tle is known about the physiological role of lipin-2, the predominant lipin protein present in liver

229 As lipin-2-deficient mice aged, they developed ataxia and i

230 Similar to patients with Majeed syndrome, lipin-2-deficient mice developed anemia, but did not sho

231 Furthermore, lipin-2-deficient mice exhibit increased sensitivity to

232 By using lipin-2-deficient mice, we uncovered a functional relati

233 generated lipin 1 that contained the PBD of lipin 3 and vice versa.

234 on does not affect the catalytic activity of lipin 3 or its ability to associate with PA in vitro The

235 The lipin 1 enzyme with the lipin 3 PBD lost its ability to be regulated by phosphor

236 nversely, the presence of the lipin 1 PBD in lipin 3 subjected the enzyme to negative intramolecular

237 in a reciprocal increase of lipin 2, but not lipin 3.

238 The genes for lipin-1, lipin-2 and lipin-3 are expressed in key metabolic tissues, includin

239 Mammalian lipins (lipin-1, lipin-2, and lipin-3) are Mg2+-dependent phosphatidate phosphatase (P

240 AP activity supplied by lipin-1, lipin-2, or lipin-3, but not lipin-1 coactivator activity, can rescu

241 2 genes encoding proteins known to activate lipin, a lipodystrophy locus in mice, and 16 other genes

242 cally normal divisions with the S. japonicus lipin acquiring an S. pombe-like mitotic phosphorylation

243 These findings suggest that lipins activate a PKC-dependent pathway during mitotic l

244 Although the c-Fos domain involved in lipin activation is its basic domain, the interaction do

245 ed from yeast to humans and functions in the lipin activation pathway.

246 ggest that the regulatory networks governing lipin activity diverged in evolution to give rise to str

247 The regulation of lipin activity may govern the pathways by which these li

248 ctively, these results show that Arabidopsis lipins, along with PDAT1 and SDP1, function synergistica

249 on to their roles during early adipogenesis, lipins also have a role in lipid droplet biogenesis.

250 Lipins are evolutionarily conserved Mg(2+)-dependent pho

251 Lipins are evolutionarily conserved phosphatidate phosph

252 Lipins are evolutionarily conserved proteins found from

253 Unlike other enzymes in the Kennedy pathway, lipins are not integral membrane proteins, and they need

254 Lipins are phosphatidate phosphatases that generate diac

255 Lipins are phosphatidic acid phosphatases with a pivotal

256 nd the results highlight a specific role for lipins as determinants of levels of a phosphatidic acid

257 e abolishes PAP activity but does not impair lipin association with microsomal membranes, the major s

258 The role of lipins at later stages of adipogenesis, when cells initi

259 ore, the delay of lamin B1 disassembly after lipin depletion could be rescued by the addition of DAG.

260 Lipins do not contain recognized membrane-association do

261 mediated depletion or chemical inhibition of lipins, enzymes that produce DAG, delayed lamin disassem

262 Another member of the lipin family (lipin 2) is enriched in liver, and hepatic

263 ortant for a deeper understanding of how the lipin family functions with respect to lipid synthesis a

264 nctional interactions between members of the lipin family in vivo, and a unique role for lipin-2 in c

265 The lipin family is a magnesium-dependent type I PA phosphat

266 ings in the field that demonstrate roles for lipin family members in metabolic homeostasis and in rar

267 Lipin-2 is a member of the lipin family of enzymes, which are key effectors in the

268 urther studies of conserved functions of the lipin family of metabolic regulators.

269 The lipin family of PA phosphatases is composed of lipins 1-

270 Pah1p is the single yeast homologue of the Lipin family of PA phosphatases.

271 d1, the phosphatidic acid phosphatase of the lipin family, by CDK phosphorylation is both necessary a

272 The lipin gene family encodes a class of Mg(2+)-dependent ph

273 e evidence implicating genetic variations in lipin genes in common metabolic dysregulation such as ob

274 ER membranes are formed due to deletion of a lipin homolog, which is responsible for de novo lipid sy

275 We also show that two Arabidopsis thaliana lipin homologs provide most of the diacylglycerol for TA

276 thermore, the key lipid metabolizing enzyme, lipin, is mislocalized in dTorsin-KO cells, and dTorsin

277 Mammalian lipins (lipin-1, lipin-2, and lipin-3) are Mg2+-dependen

278 Translocation of lipins on membranes requires their dephosphorylation by

279 Here we show that the single lipin orthologue of Drosophila melanogaster (dLipin) is

280 nt in the carboxy-terminal ends of all yeast lipin orthologues.

281 he carboxy-terminal acidic tail of the yeast lipin Pah1p as an important regulator of this step.

282 In this study, we report that yeast lipin, Pah1p, controls the formation of cytosolic lipid

283 The three lipin phosphatidate phosphatase (PAP) enzymes catalyze a

284 a mechanism for the observed differences in lipin phosphoregulation in vitro.

285 We generated 3T3-L1 cells where total lipin protein and PAP activity levels are down-regulated

286 There are three lipin protein family members in mammals and one or two o

287 ysiological role of lipin-2, the predominant lipin protein present in liver and the deficient gene pr

288 The family of three lipin proteins act as phosphatidate phosphatase (PAP) en

289 Mammalian lipin proteins also possess transcriptional coactivator

290 The lipin proteins are evolutionarily conserved proteins wit

291 ts ability to associate with PA in vitro The lipin proteins each contain a conserved polybasic domain

292 Mammalian and yeast lipin proteins have been shown to control gene expressio

293 Lipin proteins have phosphatidate phosphatase activity a

294 that provide information about the roles of lipin proteins in metabolism and human disease.

295 ation of two distinct molecular functions of lipin proteins.

296 The different lipins showed distinct tissue expression patterns.

297 O cells, and dTorsin increases levels of the lipin substrate, phosphatidate, and reduces the product,

298 ER-associated phosphatidic acid phosphatase lipin that promotes synthesis of major membrane phosphol

299 nds and dephosphorylates substrates, such as lipins, that SVST does not.

300 ng mTORC2, we overexpressed GPAT1, AGPAT, or lipin to increase the cellular content of lysophosphatid