Angiopoietin-like protein 8 regulatory pathway (WP3915)
Homo sapiens
The hepatic ANGPTL8 (Angiopoietin Like Protein 8) regulatory pathway represents an up-to-date curated interactive pathway for all of the interactions from the known regulators of ANGPTL8 and updated signaling events of insulin signaling in the liver. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP3915 CPTAC Assay Portal]
Authors
Amnah Siddiqa , Susan Coort , Elisa Cirillo , Kristina Hanspers , Egon Willighagen , Alex Pico , Marvin Martens , Eric Weitz , and Friederike EhrhartActivity
Discuss this pathway
Check for ongoing discussions or start your own.
Cited In
- Deciphering the expression dynamics of ANGPTL8 associated regulatory network in insulin resistance using formal modelling approaches (2020).
- Biological Pathways Leading From ANGPTL8 to Diabetes Mellitus–A Co-expression Network Based Analysis (2018).
- From SNPs to pathways: Biological interpretation of type 2 diabetes (T2DM) genome wide association study (GWAS) results (2018).
Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.
Organisms
Homo sapiensCommunities
Annotations
Pathway Ontology
angiopoietin signaling pathway insulin signaling pathway regulatory pathwayCell Type Ontology
hepatocyteLabel | Type | Compact URI | Comment |
---|---|---|---|
PI(3,4,5)P3 | Metabolite | kegg.compound:C05981 | Phosphatidylinositol-3,4,5-trisphosphate(PIP3) |
X-5-P | Metabolite | kegg.compound:C00231 | |
PI(4,5)P2 | Metabolite | kegg.compound:C04637 | |
Glucose | Metabolite | kegg.compound:C00031 | |
glycogen | Metabolite | kegg.compound:C00369 | |
G-6-P | Metabolite | kegg.compound:C00092 | |
amino acids | Metabolite | chebi:33709 | |
F-2,6-P2 | Metabolite | kegg.compound:C00665 | |
T3 | Metabolite | chemspider:5707 | |
T4 | Metabolite | hmdb:HMDB0000248 | |
PIK3CD | GeneProduct | ncbigene:5293 | |
PIK3C3 | GeneProduct | ncbigene:5289 | |
PTP | GeneProduct | ncbigene:5770 | PTPs catalyze the hydrolysis of the phosphate monoesters specifically on tyrosine residues. Members of the PTP family share a highly conserved catalytic motif, which is essential for the catalytic activity. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP has been shown to act as a negative regulator of insulin signaling by dephosphorylating the phosphotryosine residues of insulin receptor kinase |
IRS1 | GeneProduct | ncbigene:3667 | |
GLUT1 | GeneProduct | ncbigene:6513 | |
FBP | GeneProduct | ncbigene:2203 | |
GS | GeneProduct | ncbigene:2997 | |
RHEB | GeneProduct | ncbigene:6009 | |
G6PC | GeneProduct | ncbigene:2538 | |
PIK3R3 | GeneProduct | ncbigene:8503 | |
PIK3R1 | GeneProduct | ncbigene:5295 | |
PEPCK | GeneProduct | ncbigene:5105 | |
IRS2 | GeneProduct | ncbigene:8660 | |
PIK3C2G | GeneProduct | ncbigene:5288 | |
PIK3R2 | GeneProduct | ncbigene:5296 | |
INSR | GeneProduct | ncbigene:3643 | |
RPS6KB2 | GeneProduct | ncbigene:6199 | |
SOS1 | GeneProduct | ncbigene:6654 | |
PIK3CG | GeneProduct | ncbigene:5294 | |
IRS4 | GeneProduct | ncbigene:8471 | |
TSC2 | GeneProduct | ncbigene:7249 | |
PIK3CB | GeneProduct | ncbigene:5291 | |
SIN1 | GeneProduct | ncbigene:79109 | |
CHREBP | GeneProduct | ncbigene:51085 | |
GLUT4 | GeneProduct | ncbigene:6517 | |
CIP42 | GeneProduct | ncbigene:9322 | |
TSC1 | GeneProduct | ncbigene:7248 | |
Raptor | GeneProduct | ncbigene:57521 | |
RPS6KB1 | GeneProduct | ncbigene:6198 | |
SREBP1a-c | GeneProduct | ensembl:ENSG00000072310 | |
LPL | GeneProduct | ncbigene:4023 | |
mlst8 | GeneProduct | ncbigene:64223 | |
GCK | GeneProduct | kegg.genes:2645 | |
Rictor | GeneProduct | ncbigene:253260 | |
PIK3R4 | GeneProduct | ncbigene:30849 | |
RAS | GeneProduct | ncbigene:3265 | |
LXR | GeneProduct | ncbigene:10062 | |
SOS2 | GeneProduct | ncbigene:6655 | |
Exo70 | GeneProduct | ncbigene:23265 | |
RAF1 | GeneProduct | ncbigene:5894 | |
SREBP2 | GeneProduct | ensembl:ENSG00000198911 | |
mTOR | GeneProduct | ncbigene:2475 | |
SEST3 | GeneProduct | ncbigene:143686 | |
PIK3C2A | GeneProduct | ncbigene:5286 | |
PIK3CA | GeneProduct | ncbigene:5290 | |
DIO2 | GeneProduct | ncbigene:1734 | |
RXRA | GeneProduct | ncbigene:6256 | |
THRA | GeneProduct | ncbigene:7067 | |
THRB | GeneProduct | ncbigene:7068 | |
SLC16A2 | GeneProduct | ncbigene:6567 | |
SLCO1C1 | GeneProduct | ncbigene:53919 | |
ANGPTL8 | GeneProduct | ncbigene:55908 | synonyms: RIFL; TD26; PRO1185; PVPA599; C19orf80 |
SHC2 | GeneProduct | ncbigene:25759 | |
SHC3 | GeneProduct | ncbigene:53358 | |
SHC1 | GeneProduct | ncbigene:6464 | |
GSK3A | GeneProduct | ncbigene:2931 | |
GSK3B | GeneProduct | ncbigene:2932 | |
PDK | GeneProduct | ncbigene:5170 | |
AKT1 | GeneProduct | ncbigene:207 | |
AKT2 | GeneProduct | ncbigene:208 | |
EIF4E | GeneProduct | ncbigene:1977 | |
EIF4EBP1 | GeneProduct | ncbigene:1978 | |
FOXO1A | GeneProduct | ncbigene:2308 | |
FOXO3A | GeneProduct | ncbigene:2309 | |
CAP1 | GeneProduct | ncbigene:10487 | |
CBL | GeneProduct | ncbigene:867 | |
FLOT1 | GeneProduct | ncbigene:10211 | |
FLOT2 | GeneProduct | ncbigene:2319 | |
CRK | GeneProduct | ncbigene:1398 | |
RAPGEF1 | GeneProduct | ncbigene:2889 | |
RHOQ | GeneProduct | ncbigene:23433 | |
RXRA | GeneProduct | ensembl:ENSG00000186350 | |
ABCG8 | GeneProduct | ensembl:ENSG00000143921 | |
FASN | GeneProduct | ensembl:ENSG00000169710 | |
ABCG5 | GeneProduct | ensembl:ENSG00000138075 | |
CYP3A4 | GeneProduct | ensembl:ENSG00000160868 | |
CYP7A1 | GeneProduct | ensembl:ENSG00000167910 | is not affected in human |
CYP2B6 | GeneProduct | ensembl:ENSG00000197408 | |
SCD | GeneProduct | ensembl:ENSG00000099194 | |
MAP2K1 | GeneProduct | ncbigene:5604 | |
MAP3K7 | GeneProduct | ncbigene:6885 | |
MAPK14 | GeneProduct | ncbigene:1432 | |
MAPK1 | GeneProduct | ncbigene:5594 | |
MAP2K2 | GeneProduct | ncbigene:5605 | |
RPS6KA5 | GeneProduct | ncbigene:9252 | |
MAP3K2 | GeneProduct | ncbigene:10746 | |
MAP3K6 | GeneProduct | ncbigene:9064 | |
MAPK8 | GeneProduct | ncbigene:5599 | |
MAP4K1 | GeneProduct | ncbigene:11184 | |
MAP3K11 | GeneProduct | ncbigene:4296 | |
MAP4K3 | GeneProduct | ncbigene:8491 | |
MAPK10 | GeneProduct | ncbigene:5602 | |
RPS6KA6 | GeneProduct | ncbigene:27330 | |
MAP2K7 | GeneProduct | ncbigene:5609 | |
MAP3K4 | GeneProduct | ncbigene:4216 | |
MAP3K1 | GeneProduct | ncbigene:4214 | |
MAP3K12 | GeneProduct | ncbigene:7786 | |
MAPK4 | GeneProduct | ncbigene:5596 | |
RPS6KA4 | GeneProduct | ncbigene:8986 | |
MAPK11 | GeneProduct | ncbigene:5600 | |
MAP4K5 | GeneProduct | ncbigene:11183 | |
MAPK6 | GeneProduct | ncbigene:5597 | |
MAP4K4 | GeneProduct | ncbigene:9448 | |
MAPK3 | GeneProduct | ncbigene:5595 | |
MAP3K14 | GeneProduct | ncbigene:9020 | |
MAPK12 | GeneProduct | ncbigene:6300 | |
MAP2K5 | GeneProduct | ncbigene:5607 | |
MAP2K4 | GeneProduct | ncbigene:6416 | |
MAPK13 | GeneProduct | ncbigene:5603 | |
RPS6KA1 | GeneProduct | ncbigene:6195 | |
RPS6KA2 | GeneProduct | ncbigene:6196 | |
MAP3K5 | GeneProduct | ncbigene:4217 | |
RPS6KA3 | GeneProduct | ncbigene:6197 | |
MAPK9 | GeneProduct | ncbigene:5601 | |
MAPK7 | GeneProduct | ncbigene:5598 | |
MAP3K3 | GeneProduct | ncbigene:4215 | |
MAP3K9 | GeneProduct | ncbigene:4293 | |
MAP3K8 | GeneProduct | ncbigene:1326 | |
MAP2K6 | GeneProduct | ncbigene:5608 | |
MAP3K13 | GeneProduct | ncbigene:9175 | |
MAP4K2 | GeneProduct | ncbigene:5871 | |
MAP2K3 | GeneProduct | ncbigene:5606 | |
MAP3K10 | GeneProduct | ncbigene:4294 | |
MINK1 | GeneProduct | ncbigene:50488 | |
CBLC | GeneProduct | ncbigene:23624 | |
CBLB | GeneProduct | ncbigene:868 | |
AMPKy3 | GeneProduct | ncbigene:53632 | |
AMPKa1 | GeneProduct | ncbigene:5562 | |
AMPKy2 | GeneProduct | ncbigene:51422 | |
AMPKy1 | GeneProduct | ncbigene:5571 | |
AMPKb2 | GeneProduct | ncbigene:5565 | |
AMPKb1 | GeneProduct | ncbigene:5564 | |
AMPKa2 | GeneProduct | ncbigene:5563 | |
Insulin | Protein | uniprot:A6XGL2 |
References
- Protein-tyrosine phosphatase 1B is a negative regulator of insulin- and insulin-like growth factor-I-stimulated signaling. Kenner KA, Anyanwu E, Olefsky JM, Kusari J. J Biol Chem. 1996 Aug 16;271(33):19810–6. PubMed Europe PMC Scholia
- Protein tyrosine phosphatase 1B interacts with the activated insulin receptor. Seely BL, Staubs PA, Reichart DR, Berhanu P, Milarski KL, Saltiel AR, et al. Diabetes. 1996 Oct;45(10):1379–85. PubMed Europe PMC Scholia
- Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha. Alessi DR, James SR, Downes CP, Holmes AB, Gaffney PR, Reese CB, et al. Curr Biol. 1997 Apr 1;7(4):261–9. PubMed Europe PMC Scholia
- Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B. Stokoe D, Stephens LR, Copeland T, Gaffney PR, Reese CB, Painter GF, et al. Science. 1997 Jul 25;277(5325):567–70. PubMed Europe PMC Scholia
- Dynamics of protein-tyrosine phosphatases in rat adipocytes. Calera MR, Vallega G, Pilch PF. J Biol Chem. 2000 Mar 3;275(9):6308–12. PubMed Europe PMC Scholia
- Insulin signalling. Bevan P. J Cell Sci. 2001 Apr;114(Pt 8):1429–30. PubMed Europe PMC Scholia
- Insulin signalling and the regulation of glucose and lipid metabolism. Saltiel AR, Kahn CR. Nature. 2001 Dec 13;414(6865):799–806. PubMed Europe PMC Scholia
- The role of hepatocyte RXR alpha in xenobiotic-sensing nuclear receptor-mediated pathways. Cai Y, Konishi T, Han G, Campwala KH, French SW, Wan YJY. Eur J Pharm Sci. 2002 Feb;15(1):89–96. PubMed Europe PMC Scholia
- Induction of human liver X receptor alpha gene expression via an autoregulatory loop mechanism. Li Y, Bolten C, Bhat BG, Woodring-Dietz J, Li S, Prayaga SK, et al. Mol Endocrinol. 2002 Mar;16(3):506–14. PubMed Europe PMC Scholia
- Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR. Handschin C, Meyer UA. Arch Biochem Biophys. 2005 Jan 15;433(2):387–96. PubMed Europe PMC Scholia
- A structural basis for constitutive activity in the human CAR/RXRalpha heterodimer. Xu RX, Lambert MH, Wisely BB, Warren EN, Weinert EE, Waitt GM, et al. Mol Cell. 2004 Dec 22;16(6):919–28. PubMed Europe PMC Scholia
- Tuberous sclerosis: a GAP at the crossroads of multiple signaling pathways. Kwiatkowski DJ, Manning BD. Hum Mol Genet. 2005 Oct 15;14 Spec No. 2:R251-8. PubMed Europe PMC Scholia
- Critical nodes in signalling pathways: insights into insulin action. Taniguchi CM, Emanuelli B, Kahn CR. Nat Rev Mol Cell Biol. 2006 Feb;7(2):85–96. PubMed Europe PMC Scholia
- The reciprocal stability of FOXO1 and IRS2 creates a regulatory circuit that controls insulin signaling. Guo S, Dunn SL, White MF. Mol Endocrinol. 2006 Dec;20(12):3389–99. PubMed Europe PMC Scholia
- IRES-mediated functional coupling of transcription and translation amplifies insulin receptor feedback. Marr MT 2nd, D’Alessio JA, Puig O, Tjian R. Genes Dev. 2007 Jan 15;21(2):175–83. PubMed Europe PMC Scholia
- Carbohydrate response element binding protein gene expression is positively regulated by thyroid hormone. Hashimoto K, Ishida E, Matsumoto S, Okada S, Yamada M, Satoh T, et al. Endocrinology. 2009 Jul;150(7):3417–24. PubMed Europe PMC Scholia
- Cellular mechanisms of insulin resistance: role of stress-regulated serine kinases and insulin receptor substrates (IRS) serine phosphorylation. Tanti JF, Jager J. Curr Opin Pharmacol. 2009 Dec;9(6):753–62. PubMed Europe PMC Scholia
- FoxOs inhibit mTORC1 and activate Akt by inducing the expression of Sestrin3 and Rictor. Chen CC, Jeon SM, Bhaskar PT, Nogueira V, Sundararajan D, Tonic I, et al. Dev Cell. 2010 Apr 20;18(4):592–604. PubMed Europe PMC Scholia
- AMPK-associated signaling to bridge the gap between fuel metabolism and hepatocyte viability. Yang YM, Han CY, Kim YJ, Kim SG. World J Gastroenterol. 2010 Aug 14;16(30):3731–42. PubMed Europe PMC Scholia
- MicroRNA hsa-miR-613 targets the human LXRα gene and mediates a feedback loop of LXRα autoregulation. Ou Z, Wada T, Gramignoli R, Li S, Strom SC, Huang M, et al. Mol Endocrinol. 2011 Apr;25(4):584–96. PubMed Europe PMC Scholia
- Interplay between FOXO, TOR, and Akt. Hay N. Biochim Biophys Acta. 2011 Nov;1813(11):1965–70. PubMed Europe PMC Scholia
- Cross-regulation of hepatic glucose metabolism via ChREBP and nuclear receptors. Poupeau A, Postic C. Biochim Biophys Acta. 2011 Aug;1812(8):995–1006. PubMed Europe PMC Scholia
- Crosstalk of thyroid hormone receptor and liver X receptor in lipid metabolism and beyond [Review]. Hashimoto K, Mori M. Endocr J. 2011;58(11):921–30. PubMed Europe PMC Scholia
- Identification of RIFL, a novel adipocyte-enriched insulin target gene with a role in lipid metabolism. Ren G, Kim JY, Smas CM. Am J Physiol Endocrinol Metab. 2012 Aug 1;303(3):E334-51. PubMed Europe PMC Scholia
- Atypical angiopoietin-like protein that regulates ANGPTL3. Quagliarini F, Wang Y, Kozlitina J, Grishin NV, Hyde R, Boerwinkle E, et al. Proc Natl Acad Sci U S A. 2012 Nov 27;109(48):19751–6. PubMed Europe PMC Scholia
- Lipasin, thermoregulated in brown fat, is a novel but atypical member of the angiopoietin-like protein family. Fu Z, Yao F, Abou-Samra AB, Zhang R. Biochem Biophys Res Commun. 2013 Jan 18;430(3):1126–31. PubMed Europe PMC Scholia
- A pathway approach to investigate the function and regulation of SREBPs. Daemen S, Kutmon M, Evelo CT. Genes Nutr. 2013 May;8(3):289–300. PubMed Europe PMC Scholia
- The Paradox of Akt-mTOR Interactions. Vadlakonda L, Dash A, Pasupuleti M, Anil Kumar K, Reddanna P. Front Oncol. 2013 Jun 20;3:165. PubMed Europe PMC Scholia
- Chromosome 19 open reading frame 80 is upregulated by thyroid hormone and modulates autophagy and lipid metabolism. Tseng YH, Ke PY, Liao CJ, Wu SM, Chi HC, Tsai CY, et al. Autophagy. 2014 Jan;10(1):20–31. PubMed Europe PMC Scholia
- Betatrophin: A liver-derived hormone for the pancreatic β-cell proliferation. Raghow R. World J Diabetes. 2013 Dec 15;4(6):234–7. PubMed Europe PMC Scholia
- Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity. Fu Z, Berhane F, Fite A, Seyoum B, Abou-Samra AB, Zhang R. Sci Rep. 2014 May 23;4:5013. PubMed Europe PMC Scholia
- In vivo targeted delivery of ANGPTL8 gene for beta cell regeneration in rats. Chen J, Chen S, Huang P, Meng XL, Clayton S, Shen JS, et al. Diabetologia. 2015 May;58(5):1036–44. PubMed Europe PMC Scholia
- A Positive Feedback Loop between Akt and mTORC2 via SIN1 Phosphorylation. Yang G, Murashige DS, Humphrey SJ, James DE. Cell Rep. 2015 Aug 11;12(6):937–43. PubMed Europe PMC Scholia
- AMP-activated protein kinase suppresses the expression of LXR/SREBP-1 signaling-induced ANGPTL8 in HepG2 cells. Lee J, Hong SW, Park SE, Rhee EJ, Park CY, Oh KW, et al. Mol Cell Endocrinol. 2015 Oct 15;414:148–55. PubMed Europe PMC Scholia
- ANGPTL8/betatrophin alleviates insulin resistance via the Akt-GSK3β or Akt-FoxO1 pathway in HepG2 cells. Rong Guo X, Li Wang X, Chen Y, Hong Yuan Y, Mei Chen Y, Ding Y, et al. Exp Cell Res. 2016 Jul 15;345(2):158–67. PubMed Europe PMC Scholia
- Transcriptional regulation of hepatic lipogenesis. Wang Y, Viscarra J, Kim SJ, Sul HS. Nat Rev Mol Cell Biol. 2015 Nov;16(11):678–89. PubMed Europe PMC Scholia
- Coupling between Nutrient Availability and Thyroid Hormone Activation. Lartey LJ, Werneck-de-Castro JP, O-Sullivan I, Unterman TG, Bianco AC. J Biol Chem. 2015 Dec 18;290(51):30551–61. PubMed Europe PMC Scholia
- Angiopoietin-like protein 8 (betatrophin) is a stress-response protein that down-regulates expression of adipocyte triglyceride lipase. Zhang Y, Li S, Donelan W, Xie C, Wang H, Wu Q, et al. Biochim Biophys Acta. 2016 Feb;1861(2):130–7. PubMed Europe PMC Scholia
- Resolving Discrepant Findings on ANGPTL8 in β-Cell Proliferation: A Collaborative Approach to Resolving the Betatrophin Controversy. Cox AR, Barrandon O, Cai EP, Rios JS, Chavez J, Bonnyman CW, et al. PLoS One. 2016 Jul 13;11(7):e0159276. PubMed Europe PMC Scholia