ライフサイエンスコーパス: lipin

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

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

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

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

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

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

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

8 Mutations in human lipin 1 are a common cause of recurrent rhabdomyolysis i

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

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

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

12 but have distinct tissue distributions, with lipin 1 being the predominant PAP enzyme in many metabol

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

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

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

16 Mice with constitutive whole-body lipin 1 deficiency have been used to examine mechanisms

17 odel for determining the mechanisms by which lipin 1 deficiency leads to myocyte injury and for testi

18 e been used to examine mechanisms connecting lipin 1 deficiency to myocyte injury.

19 2 protein content was markedly increased by lipin 1 deficiency, food deprivation, and obesity, often

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

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

22 Phosphorylation of lipin 1 governs whether it is associated with the cytopl

23 l (TAG) synthesis from glycerol 3-phosphate, lipin 1 has been the focus of most of the lipin-related

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

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

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

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

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

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

37 The mammalian lipin 1 phosphatidate phosphatase is a key regulatory en

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

39 cial upstream signaling component regulating lipin 1 phosphorylation.

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

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

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

43 Lipin 1 regulates glycerolipid homeostasis by acting as

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 The importance of lipin 1 to lipid metabolism is exemplified by cellular d

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

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

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

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

52 While all lipins (lipin 1, 2, and 3) act as phosphatidic acid phosphatase

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

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

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 The 3 lipin proteins (lipin 1, lipin 2, and lipin 3) each have PAP activity, b

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

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

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

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

62 Additionally, lipin 1-deficient mice had abundant, but abnormal, mitoc

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

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

65 These data suggest that mice lacking lipin 1-mediated PAP activity in skeletal muscle may ser

66 Loss of lipin 1-mediated phosphatidic acid phosphohydrolase acti

67 e cytoplasmic localization of phosphorylated lipin 1.

68 ee of phosphorylation-mediated regulation of lipin 1.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

85 Lipin-1 catalyzes the formation of diacylglycerol from p

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

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

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

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

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

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

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

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

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

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

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

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

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

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

104 3-3 promotes the cytoplasmic localization of lipin-1 in 3T3-L1 adipocytes.

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

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

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

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

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

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

111 Lipin-1 is a phosphatidate phosphatase in glycerolipid b

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

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

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

115 Lipin-1 is critical for lipid synthesis and homeostasis

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

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

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

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

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

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

122 1 and binds well to the non-phosphorylatable lipin-1 mutant.

123 Lipin-1 mutations cause lipodystrophy in mice and acute

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

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

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

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

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

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

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

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

132 Lipin-1 regulation of phospholipid synthesis maintains e

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

150 on and phosphatidate phosphatase activity of lipin-1.

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

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

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

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

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

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

157 Mutational analysis of lipin 1beta and its peptides indicated that Ser-285 and

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

159 Here, we demonstrate that lipin 1beta is a bona fide substrate for casein kinase I

160 sis and phosphopeptide mapping revealed that lipin 1beta is phosphorylated by CKII on multiple serine

161 Lipin 1beta is phosphorylated on multiple sites, but les

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

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

164 our understanding of how phosphorylation of lipin 1beta phosphatidate phosphatase regulates its inte

165 atable alanine attenuated the interaction of lipin 1beta with 14-3-3beta protein, a regulatory hub th

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

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

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

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

170 sue of the JCI, Zhang et al. show that while lipin 2 and 3 are expendable for the incorporation of di

171 e, which is unique in expressing exclusively lipin 2 and lipin 3.

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

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

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

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

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

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

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

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

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

181 The 3 lipin proteins (lipin 1, lipin 2, and lipin 3) each have PAP activity, but have d

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

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

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

185 These data implicate lipin 2/3 as a control point for enterocyte phospholipid

186 Lipin 2/3 deficiency caused phosphatidic acid accumulati

187 Impaired chylomicron synthesis in lipin 2/3 deficiency could be rescued by normalizing pho

188 n of dietary fatty acids into triglycerides, lipin 2/3 PAP activity has a critical role in phospholip

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

190 Lipin-2 also inhibits the activation and sensitization o

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

209 An N-Lip C-Lip fusion of mouse lipin-2 is catalytically active, which suggests mammalia

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

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

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

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

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

215 Lipin-2 regulates MAPK activation, which mediates synthe

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

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

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

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

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

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

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

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

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

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

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

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

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

229 The 3 lipin proteins (lipin 1, lipin 2, and lipin 3) each have PAP activity, but have distinct tissu

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

231 unique in expressing exclusively lipin 2 and lipin 3.

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

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

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

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

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

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

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

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

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

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

242 Lipins are evolutionarily conserved phosphatidate phosph

243 Lipins are evolutionarily conserved proteins found from

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

245 Lipins are phosphatidate phosphatases that generate diac

246 Lipins are phosphatidic acid phosphatases with a pivotal

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

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

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

250 Lipins do not contain recognized membrane-association do

251 We determined that lipin enzymes are critical for chylomicron biogenesis, t

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

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

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

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

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

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

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

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

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

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

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

263 talytically active, which suggests mammalian lipins function with the same domain architecture as Tt

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

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

266 Pah1 is the yeast lipin homolog of mice and humans.

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

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

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

270 While all lipins (lipin 1, 2, and 3) act as phosphatidic acid phos

271 Translocation of lipins on membranes requires their dephosphorylation by

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

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

274 This illustrates mechanisms for lipin/Pah PAP function, membrane association, and lipin-

275 Lipin/Pah phosphatidic acid phosphatases (PAPs) generate

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

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

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

279 The lipin phosphatidic acid phosphatase (PAP) enzymes are re

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

281 Lipins play important roles in adipogenesis, insulin sen

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

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

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

285 The 3 lipin proteins (lipin 1, lipin 2, and lipin 3) each have

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

287 Mammalian lipin proteins also possess transcriptional coactivator

288 The lipin proteins are evolutionarily conserved proteins wit

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

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

291 Lipin proteins have phosphatidate phosphatase activity a

292 require the PAP reaction, making the role of lipin proteins in enterocytes unclear.

293 ation of two distinct molecular functions of lipin proteins.

294 /Pah PAP function, membrane association, and lipin-related pathologies.

295 e, lipin 1 has been the focus of most of the lipin-related research.

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

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

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

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

300 trols de novo glycerolipid synthesis through lipin to prevent invasion of excess ER membranes into NE