Details of Protein

General Information of Protein (ID: PRT01262)
Name Signal-regulated kinase 2 (ERK2)
Synonyms   Click to Show/Hide Synonyms of This Protein
MAP kinase 1; MAPK 1; ERT1; Extracellular signal-regulated kinase 2; ERK-2; MAP kinase isoform p42; p42-MAPK; Mitogen-activated protein kinase 2; MAP kinase 2; MAPK 2; MAPK1; ERK2; PRKM1; PRKM2
Gene Name MAPK1 Gene ID
5594
UniProt ID
P28482
Family Transferases (EC 2)
EC Number   EC: 2.7.11.24  (Click to Show/Hide the Complete EC Tree)
Transferase
Kinase
Protein-serine/threonine kinases
EC: 2.7.11.24
  Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Function) of This Protein
Sequence
MAAAAAAGAGPEMVRGQVFDVGPRYTNLSYIGEGAYGMVCSAYDNVNKVRVAIKKISPFE
HQTYCQRTLREIKILLRFRHENIIGINDIIRAPTIEQMKDVYIVQDLMETDLYKLLKTQH
LSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTTCDLKICDFGLARVADPDHDH
TGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHI
LGILGSPSQEDLNCIINLKARNYLLSLPHKNKVPWNRLFPNADSKALDLLDKMLTFNPHK
RIEVEQALAHPYLEQYYDPSDEPIAEAPFKFDMELDDLPKEKLKELIFEETARFQPGYRS
Structure
1PME ; 1TVO ; 1WZY ; 2OJG ; 2OJI ; 2OJJ ; 2Y9Q ; 3D42 ; 3D44 ; 3I5Z ; 3I60 ; 3SA0 ; 3TEI ; 3W55 ; 4FMQ ; 4FUX ; 4FUY ; 4FV0 ; 4FV1 ; 4FV2 ; 4FV3 ; 4FV4 ; 4FV5 ; 4FV6 ; 4FV7 ; 4FV8 ; 4FV9 ; 4G6N ; 4G6O ; 4H3P ; 4H3Q ; 4IZ5 ; 4IZ7 ; 4IZA ; 4N0S ; 4NIF ; 4O6E ; 4QP1 ; 4QP2 ; 4QP3 ; 4QP4 ; 4QP6 ; 4QP7 ; 4QP8 ; 4QP9 ; 4QPA ; 4QTA ; 4QTE ; 4XJ0 ; 4ZXT ; 4ZZM ; 4ZZN ; 4ZZO ; 5AX3 ; 5BUE ; 5BUI ; 5BUJ ; 5BVD ; 5BVE ; 5BVF ; 5K4I ; 5LCJ ; 5LCK ; 5NGU ; 5NHF ; 5NHH ; 5NHJ ; 5NHL ; 5NHO ; 5NHP ; 5NHV ; 5V60 ; 5V61 ; 5V62 ; 5WP1 ; 6D5Y ; 6DMG ; 6G54 ; 6G8X ; 6G91 ; 6G92 ; 6G93 ; 6G97 ; 6G9A ; 6G9D ; 6G9H ; 6G9J ; 6G9K ; 6G9M ; 6G9N ; 6GDM ; 6GDQ ; 6GE0 ; 6GJB ; 6GJD ; 6NBS ; 6OPG ; 6OPH ; 6OPI ; 6Q7K ; 6Q7S ; 6Q7T ; 6QA1 ; 6QA3 ; 6QA4 ; 6QAG ; 6QAH ; 6QAL ; 6QAQ ; 6QAW ; 6RQ4 ; 6SLG
Function Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in respons to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2.; Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.
Regulatory Network
Full List of Metabolite(s) Regulating This Protein
      Nucleosides, nucleotides, and analogues
            UDP glucose Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation UDP glucose addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Acute lymphoblastic leukemia [ICD-11: 2B33]
                      Details It is reported that UDP glucose addition causes the increase of MAPK1 protein phosphorylation compared with control group.
            Uridine 5'-diphosphate Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Uridine 5'-diphosphate addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Acute lymphoblastic leukemia [ICD-11: 2B33]
                      Details It is reported that uridine 5'-diphosphate addition causes the increase of MAPK1 protein phosphorylation compared with control group.
      Homogeneous metal compounds
            Calcium Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Calcium addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that calcium addition causes the increase of MAPK1 protein phosphorylation compared with control group.
            Gadolinium Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Gadolinium addition (0.17 hour)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that gadolinium addition causes the increase of MAPK1 protein phosphorylation compared with control group.
            Magnesium Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Magnesium addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that magnesium addition causes the increase of MAPK1 protein phosphorylation compared with control group.
      Lipids and lipid-like molecules
            1-Oleoyl LPI Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation 1-Oleoyl LPI addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that 1-oleoyl LPI addition causes the increase of MAPK1 protein phosphorylation compared with control group.
            1-Palmitoyl LPI Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation 1-Palmitoyl LPI addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that 1-palmitoyl LPI addition causes the increase of MAPK1 protein phosphorylation compared with control group.
            1-Stearoyl LPI Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation 1-Stearoyl LPI addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that 1-stearoyl LPI addition causes the increase of MAPK1 protein phosphorylation compared with control group.
            12-HETE Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [4]
                      Introduced Variation 12-HETE addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that 12-HETE addition causes the increase of MAPK1 protein phosphorylation compared with control group.
            2-Arachidonoyl-LPI Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation 2-Arachidonoyl-LPI addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that 2-arachidonoyl-LPI addition causes the increase of MAPK1 protein phosphorylation compared with control group.
            2-Linoleoyl LPI Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation 2-Linoleoyl LPI addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that 2-linoleoyl LPI addition causes the increase of MAPK1 protein phosphorylation compared with control group.
            2-Oleoyl LPI Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation 2-Oleoyl LPI addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that 2-oleoyl LPI addition causes the increase of MAPK1 protein phosphorylation compared with control group.
            2-Oleoyl-LPA Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [5]
                      Introduced Variation 2-Oleoyl-LPA addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Stomach cancer [ICD-11: 2B72]
                      Details It is reported that 2-oleoyl-LPA addition causes the increase of MAPK1 protein phosphorylation compared with control group.
            5-oxo-ETE Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [6]
                      Introduced Variation 5-oxo-ETE addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Pulmonary hypertension [ICD-11: BB01]
                      Details It is reported that 5-oxo-ETE addition causes the increase of MAPK1 protein phosphorylation compared with control group.
            Hydroxyoctanoic acid Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [7]
                      Introduced Variation Hydroxyoctanoic acid addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Diabetic acidosis [ICD-11: 5A22]
                      Details It is reported that hydroxyoctanoic acid addition causes the increase of MAPK1 protein phosphorylation compared with control group.
            LysoPA(18:1(9Z)/0:0) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [8]
                      Introduced Variation LysoPA(18:1(9Z)/0:0) addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Idiopathic pulmonary fibrosis [ICD-11: CB03] ...
                      Details It is reported that lysoPA(18:1(9Z)/0:0) addition causes the increase of MAPK1 protein phosphorylation compared with control group.
            LysoPG(16:0/0:0) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation LysoPG(16:0/0:0) addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that lysoPG(16:0/0:0) addition causes the increase of MAPK1 protein phosphorylation compared with control group.
            LysoPS(18:0/0:0) Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [9]
                      Introduced Variation LysoPS(18:0/0:0) addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Anaphylaxis [ICD-11: 4A84]
                      Details It is reported that lysoPS(18:0/0:0) addition causes the increase of MAPK1 protein phosphorylation compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [10]
                      Introduced Variation LysoPS(18:0/0:0) addition (0.5 hour)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Inflammatory bowel disease [ICD-11: DD72]
                      Details It is reported that lysoPS(18:0/0:0) addition causes the increase of MAPK1 protein phosphorylation compared with control group.
            Resolvin E1 Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [11]
                      Introduced Variation Resolvin E1 addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Coronary artery disease [ICD-11: BA80]
                      Details It is reported that resolvin E1 addition causes the increase of MAPK1 protein phosphorylation compared with control group.
      Organic acids and derivatives
            Leucine Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [12]
                      Introduced Variation Leucine addition (5 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that leucine addition causes the increase of MAPK1 protein phosphorylation compared with control group.
            N-Arachidonoylglycine Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [13]
                      Introduced Variation N-Arachidonoylglycine addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Endometriosis [ICD-11: GA10]
                      Details It is reported that N-arachidonoylglycine addition causes the increase of MAPK1 protein phosphorylation compared with control group.
            Phenylalanine Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [14]
                      Introduced Variation Phenylalanine addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Diabetes mellitus [ICD-11: 5A14]
                      Details It is reported that phenylalanine addition causes the increase of MAPK1 protein phosphorylation compared with control group.
      Organic nitrogen compounds
            Anandamide Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [13]
                      Introduced Variation Anandamide addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Endometriosis [ICD-11: GA10]
                      Details It is reported that anandamide addition causes the increase of MAPK1 protein phosphorylation compared with control group.
      Organic oxygen compounds
            Glucose Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [15]
                      Introduced Variation Glucose addition (50 hours)
                      Induced Change MAPK1 protein abundance levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Brain cancer [ICD-11: 2A00]
                      Details It is reported that glucose addition causes the increase of MAPK1 protein abundance compared with control group.
      Organoheterocyclic compounds
            Tryptophan Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [14]
                      Introduced Variation Tryptophan addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Diabetes mellitus [ICD-11: 5A14]
                      Details It is reported that tryptophan addition causes the increase of MAPK1 protein phosphorylation compared with control group.
References
1 Quantification of Gi-mediated inhibition of adenylyl cyclase activity reveals that UDP is a potent agonist of the human P2Y14 receptor. Mol Pharmacol. 2009 Dec;76(6):1341-8.
2 Identification of a novel extracellular cation-sensing G-protein-coupled receptor. J Biol Chem. 2005 Dec 2;280(48):40201-9.
3 2-Arachidonoyl-sn-glycero-3-phosphoinositol: a possible natural ligand for GPR55. J Biochem. 2009 Jan;145(1):13-20.
4 Identification of the orphan G protein-coupled receptor GPR31 as a receptor for 12-(S)-hydroxyeicosatetraenoic acid. J Biol Chem. 2011 Sep 30;286(39):33832-40.
5 GPR35 is a novel lysophosphatidic acid receptor. Biochem Biophys Res Commun. 2010 Apr 30;395(2):232-7.
6 TG1019/OXE, a Galpha(i/o)-protein-coupled receptor, mediates 5-oxo-eicosatetraenoic acid-induced chemotaxis. Biochem Biophys Res Commun. 2005 Sep 9;334(4):987-95.
7 Deorphanization of GPR109B as a receptor for the beta-oxidation intermediate 3-OH-octanoic acid and its role in the regulation of lipolysis. J Biol Chem. 2009 Aug 14;284(33):21928-21933.
8 Antidepressants induce profibrotic responses via the lysophosphatidic acid receptor LPA 1. Eur J Pharmacol. 2020 Apr 15;873:172963.
9 Identification of a lysophosphatidylserine receptor on mast cells. Biochem Biophys Res Commun. 2006 Mar 24;341(4):1078-87.
10 Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35. J Biol Chem. 2006 Aug 4;281(31):22021-22028.
11 Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J Exp Med. 2005 Mar 7;201(5):713-22.
12 Influence of leucine on protein metabolism, phosphokinase expression, and cell proliferation in human duodenum1,3. Am J Clin Nutr. 2011 Jun;93(6):1255-62.
13 (9) -Tetrahydrocannabinol and N-arachidonyl glycine are full agonists at GPR18 receptors and induce migration in human endometrial HEC-1B cells. Br J Pharmacol. 2012 Apr;165(8):2414-24.
14 Computer-aided discovery of aromatic l--amino acids as agonists of the orphan G protein-coupled receptor GPR139. J Chem Inf Model. 2014 Jun 23;54(6):1553-7.
15 Glucose deprivation activates a metabolic and signaling amplification loop leading to cell death. Mol Syst Biol. 2012 Jun 26;8:589.

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