Adrenoceptor beta 2, surface |
Crystallographic structure of the β2-adrenergic receptor depicted as a green cartoon and the bound partial inverse agonist carazolol ligand as spheres (carbon atom = grey, oxygen = red, nitrogen = blue). The phospholipid bilayer is depicted as blue spheres (phosphate head groups) and yellow lines (lipid sidechains).[1][2] |
Available structures |
PDB |
Ortholog search: PDBe, RCSB |
List of PDB id codes |
1GQ4, 2R4R, 2R4S, 2RH1, 3D4S, 3KJ6, 3NY8, 3NY9, 3NYA, 3P0G, 3PDS, 3SN6, 4GBR
|
|
|
Identifiers |
Symbols |
ADRB2; ADRB2R; ADRBR; B2AR; BAR; BETA2AR |
External IDs |
OMIM: 109690 MGI: 87938 HomoloGene: 30948 IUPHAR: β2-adrenoceptor ChEMBL: 210 GeneCards: ADRB2 Gene |
Gene Ontology |
Molecular function |
• beta2-adrenergic receptor activity
• protein binding
• drug binding
• adenylate cyclase binding
• potassium channel regulator activity
• dopamine binding
• ionotropic glutamate receptor binding
• protein homodimerization activity
• epinephrine binding
• norepinephrine binding
|
Cellular component |
• nucleus
• lysosome
• endosome
• plasma membrane
• integral to plasma membrane
• caveola
• apical plasma membrane
• axon
• neuronal cell body membrane
• sarcolemma
• dendritic spine
• receptor complex
|
Biological process |
• diet induced thermogenesis
• vasodilation by norepinephrine-epinephrine involved in regulation of systemic arterial blood pressure
• desensitization of G-protein coupled receptor protein signaling pathway by arrestin
• diaphragm contraction
• positive regulation of the force of heart contraction by epinephrine
• receptor-mediated endocytosis
• cell surface receptor signaling pathway
• activation of transmembrane receptor protein tyrosine kinase activity
• adenylate cyclase-modulating G-protein coupled receptor signaling pathway
• adenylate cyclase-activating G-protein coupled receptor signaling pathway
• activation of adenylate cyclase activity
• positive regulation of cell proliferation
• endosome to lysosome transport
• response to cold
• positive regulation of sodium ion transport
• negative regulation of ossification
• positive regulation of bone mineralization
• positive regulation of protein ubiquitination
• heat generation
• synaptic transmission, glutamatergic
• negative regulation of urine volume
• negative regulation of multicellular organism growth
• wound healing
• positive regulation of apoptotic process
• positive regulation of potassium ion transport
• positive regulation of MAPK cascade
• bone resorption
• positive regulation of vasodilation
• positive regulation of transcription from RNA polymerase II promoter
• negative regulation of smooth muscle contraction
• positive regulation of skeletal muscle tissue growth
• negative regulation of inflammatory response
• brown fat cell differentiation
• regulation of sensory perception of pain
• regulation of excitatory postsynaptic membrane potential
|
Sources: Amigo / QuickGO |
|
RNA expression pattern |
|
More reference expression data |
Orthologs |
Species |
Human |
Mouse |
|
Entrez |
154 |
11555 |
|
Ensembl |
ENSG00000169252 |
ENSMUSG00000045730 |
|
UniProt |
P07550 |
P18762 |
|
RefSeq (mRNA) |
NM_000024.5 |
NM_007420.2 |
|
RefSeq (protein) |
NP_000015.1 |
NP_031446.2 |
|
Location (UCSC) |
Chr 5:
148.21 – 148.21 Mb |
Chr 18:
62.18 – 62.18 Mb |
|
PubMed search |
[1] |
[2] |
|
|
The beta-2 adrenergic receptor (β2 adrenoreceptor), also known as ADRB2, is a beta-adrenergic receptor, and also denotes the human gene encoding it.[3]
Contents
- 1 Gene
- 2 Structure
- 3 Mechanism
- 4 Function
- 4.1 Muscular system
- 4.2 Circulatory system
- 4.3 Eye
- 4.4 Digestive system
- 4.5 Other
- 5 Agonists
- 6 Antagonists
- 7 See also
- 8 Interactions
- 9 References
- 10 External links
- 11 Further reading
|
Gene
The ADRB2 gene is intronless. Different polymorphic forms, point mutations, and/or downregulation of this gene are associated with nocturnal asthma, obesity and type 2 diabetes.[4]
Structure
The 3D crystallographic structure (see figure and links to the right) of the β2-adrenergic receptor has been determined[5][1][2] by making a fusion protein with lysozyme to increase the hydrophillic surface area of the protein for crystal contacts.
Mechanism
This receptor is directly associated with one of its ultimate effectors, the class C L-type calcium channel CaV1.2. This receptor-channel complex is coupled to the Gs G protein, which activates adenylyl cyclase, catalysing the formation of cyclic adenosine monophosphate (cAMP) which then activates protein kinase A, and the counterbalancing phosphatase PP2A. The assembly of the signaling complex provides a mechanism that ensures specific and rapid signaling. A two-state biophysical and molecular model has been proposed to account for the pH and REDOX sensitivity of this and other GPCRs.[6]
Beta-2 Adrenergic Receptors have also been found to couple with Gi, possibly providing a mechanism by which response to ligand is highly localized within cells. In contrast, Beta-1 Adrenergic Receptors are coupled only to Gs, and stimulation of these results in a more diffuse cellular response.[7] This appears to be mediated by cAMP induced PKA phosphorylation of the receptor.[8]
Function
Actions of the β2 receptor include:
Muscular system
Tissue/Effect |
Function |
Smooth muscle relaxation in:
|
uterus
|
|
GI tract (decreases motility) |
Delay digestion during fight-or-flight response |
detrusor urinae muscle of bladder wall[9] This effect is stronger than the alpha-1 receptor effect of contraction.
|
Delay need of micturition |
seminal tract[10] |
|
bronchi[11] |
Facilitate respiration (agonists can be useful in treating asthma) |
- blood vessels
- dilates smaller coronary arteries[12]
- dilates hepatic artery
- dilates arteries to skeletal muscle
|
Increase perfusion of organs |
needed during fight-or-flight |
striated muscle |
Tremor[10] (via PKA mediated facilitation of presynaptic Ca2+ influx leading to acetylcholine release) |
|
Increased mass and contraction speed[10] |
fight-or-flight |
glycogenolysis[10] |
provide glucose fuel |
Circulatory system
- Heart muscle contraction
- Increase cardiac output (minor degree compared to β1).
- Increase heart rate [11] in sinoatrial node (SA node) (chronotropic effect).
- Increase atrial cardiac muscle contractility. (inotropic effect).
- Increases contractility and automaticity[11] of ventricular cardiac muscle.
- Dilate hepatic artery.
- Dilate arteries to skeletal muscle.
Eye
In the normal eye, beta-2 stimulation by salbutamol increases intraocular pressure via net:
- Increase in production of aqueous humour by the ciliary process,
- Subsequent increased pressure-dependent uveoscleral outflow of humour, despite reduced drainage of humour via the Canal of Schlemm.
In glaucoma, drainage is reduced ( open-angle glaucoma) or blocked completely (closed-angle glaucoma). In such cases, beta-2 stimulation with its consequent increase in humour production is highly contra-indicated, and conversely, a topical beta-2 antagonist such as timolol may be employed.
Digestive system
- Glycogenolysis and gluconeogenesis in liver.[11]
- Glycogenolysis and lactate release in skeletal muscle.[11]
- Contract sphincters of GI tract.
- Insulin secretion from pancreas.[11][13]
- Thickened secretions from salivary glands.[11]
Other
- Inhibit histamine-release from mast cells.
- Increase protein content of secretions from lacrimal glands.
- Increase renin secretion from kidney.
- Receptor also present in cerebellum.
- Bronchiole dilation (targeted while treating asthma attacks)
- Involved in brain - immune - communication [14]
Agonists
Main article: Beta2-adrenergic agonist
- spasmolytics in asthma and COPD
- salbutamol (albuterol in USA)
- bitolterol mesylate
- isoproterenol
- levosalbutamol (levalbuteral in USA)
- metaproterenol
- formoterol
- salmeterol
- terbutaline
- clenbuterol
- ritodrine (tocolytic)
Antagonists
(Beta blockers)
- butoxamine*[10]
- First generation (non-selective) β-blockers
* denotes selective agonists to the receptor.
See also
- Other adrenergic receptors
- Alpha-1 adrenergic receptor
- Alpha-2 adrenergic receptor
- Beta-1 adrenergic receptor
- Beta-3 adrenergic receptor
Interactions
Beta-2 adrenergic receptor has been shown to interact with Delta Opioid receptor,[15] Sodium-hydrogen antiporter 3 regulator 1,[16][17][18] AKAP12[19][20] and Grb2.[21]
References
- ^ a b PDB 2RH1; Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Kuhn P, Weis WI, Kobilka BK, Stevens RC (2007). "High-resolution crystal structure of an engineered human β2-adrenergic G protein-coupled receptor". Science 318 (5854): 1258–65. doi:10.1126/science.1150577. PMC 2583103. PMID 17962520. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2583103/.
- ^ a b Rosenbaum DM, Cherezov V, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Yao XJ, Weis WI, Stevens RC, Kobilka BK (2007). "GPCR engineering yields high-resolution structural insights into β2-adrenergic receptor function". Science 318 (5854): 1266–73. doi:10.1126/science.1150609. PMID 17962519.
- ^ "Entrez Gene: ADRB1 adrenergic, beta-1-, receptor". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=153.
- ^ "Entrez Gene: ADRB2 adrenergic, beta-2-, receptor, surface". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=154.
- ^ Rasmussen SG, Choi HJ, Rosenbaum DM, Kobilka TS, Thian FS, Edwards PC, Burghammer M, Ratnala VR, Sanishvili R, Fischetti RF, Schertler GF, Weis WI, Kobilka BK (2007). "Crystal structure of the human β2-adrenergic G-protein-coupled receptor". Nature 450 (7168): 383–7. Bibcode 2007Natur.450..383R. doi:10.1038/nature06325. PMID 17952055.
- ^ Rubenstein LA, Zauhar RJ, Lanzara RG (2006). "Molecular dynamics of a biophysical model for β2-adrenergic and G protein-coupled receptor activation". J. Mol. Graph. Model. 25 (4): 396–409. doi:10.1016/j.jmgm.2006.02.008. PMID 16574446.
- ^ Chen-Izu Y, Xiao RP, Izu LT, Cheng H, Kuschel M, Spurgeon H, Lakatta EG (November 2000). "G(i)-dependent localization of beta(2)-adrenergic receptor signaling to L-type Ca(2+) channels". Biophys. J. 79 (5): 2547–56. Bibcode 2000BpJ....79.2547C. doi:10.1016/S0006-3495(00)76495-2. PMC 1301137. PMID 11053129. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1301137/.
- ^ Zamah AM, Delahunty M, Luttrell LM, Lefkowitz RJ (August 2002). "Protein kinase A-mediated phosphorylation of the beta 2-adrenergic receptor regulates its coupling to Gs and Gi. Demonstration in a reconstituted system". J. Biol. Chem. 277 (34): 31249–56. doi:10.1074/jbc.M202753200. PMID 12063255.
- ^ von Heyden B, Riemer RK, Nunes L, Brock GB, Lue TF, Tanagho EA (1995). "Response of guinea pig smooth and striated urethral sphincter to cromakalim, prazosin, nifedipine, nitroprusside, and electrical stimulation". Neurourol. Urodyn. 14 (2): 153–68. doi:10.1002/nau.1930140208. PMID 7540086.
- ^ a b c d e Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 163
- ^ a b c d e f g Fitzpatrick, David; Purves, Dale; Augustine, George (2004). "Table 20:2". Neuroscience (Third ed.). Sunderland, Mass: Sinauer. ISBN 0-87893-725-0.
- ^ Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 270
- ^ Trovik TS, Vaartun A, Jorde R, Sager G (1995). "Dysfunction in the beta 2-adrenergic signal pathway in patients with insulin dependent diabetes mellitus (IDDM) and unawareness of hypoglycaemia". Eur. J. Clin. Pharmacol. 48 (5): 327–32. doi:10.1007/BF00194946. PMID 8641318.
- ^ Elenkov, I. J., R. L. Wilder, et al. (2000). "The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system.". Pharmacol Rev 52 (4): 595–638. PMID 11121511.
- ^ McVey, M; Ramsay D, Kellett E, Rees S, Wilson S, Pope A J, Milligan G (Apr. 2001). "Monitoring receptor oligomerization using time-resolved fluorescence resonance energy transfer and bioluminescence resonance energy transfer. The human delta -opioid receptor displays constitutive oligomerization at the cell surface, which is not regulated by receptor occupancy". J. Biol. Chem. (United States) 276 (17): 14092–9. doi:10.1074/jbc.M008902200. ISSN 0021-9258. PMID 11278447.
- ^ Karthikeyan, Subramanian; Leung Teli, Ladias John A A (May. 2002). "Structural determinants of the Na+/H+ exchanger regulatory factor interaction with the beta 2 adrenergic and platelet-derived growth factor receptors". J. Biol. Chem. (United States) 277 (21): 18973–8. doi:10.1074/jbc.M201507200. ISSN 0021-9258. PMID 11882663.
- ^ Hall, R A; Ostedgaard L S, Premont R T, Blitzer J T, Rahman N, Welsh M J, Lefkowitz R J (Jul. 1998). "A C-terminal motif found in the beta2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 95 (15): 8496–501. Bibcode 1998PNAS...95.8496H. doi:10.1073/pnas.95.15.8496. ISSN 0027-8424. PMC 21104. PMID 9671706. //www.ncbi.nlm.nih.gov/pmc/articles/PMC21104/.
- ^ Hall, R A; Premont R T, Chow C W, Blitzer J T, Pitcher J A, Claing A, Stoffel R H, Barak L S, Shenolikar S, Weinman E J, Grinstein S, Lefkowitz R J (Apr. 1998). "The beta2-adrenergic receptor interacts with the Na+/H+-exchanger regulatory factor to control Na+/H+ exchange". Nature (ENGLAND) 392 (6676): 626–30. Bibcode 1998Natur.392..626H. doi:10.1038/33458. ISSN 0028-0836. PMID 9560162.
- ^ Fan, G; Shumay E, Wang H, Malbon C C (Jun. 2001). "The scaffold protein gravin (cAMP-dependent protein kinase-anchoring protein 250) binds the beta 2-adrenergic receptor via the receptor cytoplasmic Arg-329 to Leu-413 domain and provides a mobile scaffold during desensitization". J. Biol. Chem. (United States) 276 (26): 24005–14. doi:10.1074/jbc.M011199200. ISSN 0021-9258. PMID 11309381.
- ^ Shih, M; Lin F, Scott J D, Wang H Y, Malbon C C (Jan. 1999). "Dynamic complexes of beta2-adrenergic receptors with protein kinases and phosphatases and the role of gravin". J. Biol. Chem. (UNITED STATES) 274 (3): 1588–95. doi:10.1074/jbc.274.3.1588. ISSN 0021-9258. PMID 9880537.
- ^ Karoor, V; Wang L, Wang H Y, Malbon C C (Dec. 1998). "Insulin stimulates sequestration of beta-adrenergic receptors and enhanced association of beta-adrenergic receptors with Grb2 via tyrosine 350". J. Biol. Chem. (UNITED STATES) 273 (49): 33035–41. doi:10.1074/jbc.273.49.33035. ISSN 0021-9258. PMID 9830057.
External links
- "β2-adrenoceptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2189.
Further reading
- Frielle T, Caron MG, Lefkowitz RJ (1989). "Properties of the beta 1- and beta 2-adrenergic receptor subtypes revealed by molecular cloning.". Clin. Chem. 35 (5): 721–5. PMID 2541947.
- Taylor DR, Kennedy MA (2002). "Genetic variation of the beta(2)-adrenoceptor: its functional and clinical importance in bronchial asthma.". American journal of pharmacogenomics : genomics-related research in drug development and clinical practice 1 (3): 165–74. PMID 12083965.
- Thibonnier M, Coles P, Thibonnier A, Shoham M (2002). "Molecular pharmacology and modeling of vasopressin receptors.". Prog. Brain Res. 139: 179–96. doi:10.1016/S0079-6123(02)39016-2. PMID 12436935.
- Ge D, Huang J, He J, et al. (2005). "beta2-Adrenergic receptor gene variations associated with stage-2 hypertension in northern Han Chinese.". Ann. Hum. Genet. 69 (Pt 1): 36–44. doi:10.1046/j.1529-8817.2003.00093.x. PMID 15638826.
- Muszkat M (2007). "Interethnic differences in drug response: the contribution of genetic variability in beta adrenergic receptor and cytochrome P4502C9.". Clin. Pharmacol. Ther. 82 (2): 215–8. doi:10.1038/sj.clpt.6100142. PMID 17329986.
- Bucens D, Pain MC (1976). "Influence of hematocrit, blood gas tensions, and pH on pressure-flow relations in the isolated canine lung.". Circ. Res. 37 (5): 588–96. PMID 154.
- von Zastrow M, Kobilka BK (1992). "Ligand-regulated internalization and recycling of human beta 2-adrenergic receptors between the plasma membrane and endosomes containing transferrin receptors.". J. Biol. Chem. 267 (5): 3530–8. PMID 1371121.
- Gope R, Gope ML, Thorson A, et al. (1992). "Genetic changes at the beta-2-adrenergic receptor locus on chromosome 5 in human colorectal carcinomas.". Anticancer Res. 11 (6): 2047–50. PMID 1663718.
- Bouvier M, Guilbault N, Bonin H (1991). "Phorbol-ester-induced phosphorylation of the beta 2-adrenergic receptor decreases its coupling to Gs.". FEBS Lett. 279 (2): 243–8. doi:10.1016/0014-5793(91)80159-Z. PMID 1848190.
- Yang-Feng TL, Xue FY, Zhong WW, et al. (1990). "Chromosomal organization of adrenergic receptor genes.". Proc. Natl. Acad. Sci. U.S.A. 87 (4): 1516–20. Bibcode 1990PNAS...87.1516Y. doi:10.1073/pnas.87.4.1516. PMC 53506. PMID 2154750. //www.ncbi.nlm.nih.gov/pmc/articles/PMC53506/.
- Hui KK, Yu JL (1989). "Effects of protein kinase inhibitor, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, on beta-2 adrenergic receptor activation and desensitization in intact human lymphocytes.". J. Pharmacol. Exp. Ther. 249 (2): 492–8. PMID 2470898.
- Hen R, Axel R, Obici S (1989). "Activation of the beta 2-adrenergic receptor promotes growth and differentiation in thyroid cells.". Proc. Natl. Acad. Sci. U.S.A. 86 (12): 4785–8. Bibcode 1989PNAS...86.4785H. doi:10.1073/pnas.86.12.4785. PMC 287358. PMID 2471981. //www.ncbi.nlm.nih.gov/pmc/articles/PMC287358/.
- O'Dowd BF, Hnatowich M, Caron MG, et al. (1989). "Palmitoylation of the human beta 2-adrenergic receptor. Mutation of Cys341 in the carboxyl tail leads to an uncoupled nonpalmitoylated form of the receptor.". J. Biol. Chem. 264 (13): 7564–9. PMID 2540197.
- Bristow MR, Hershberger RE, Port JD, et al. (1989). "Beta 1- and beta 2-adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium.". Mol. Pharmacol. 35 (3): 295–303. PMID 2564629.
- Emorine LJ, Marullo S, Delavier-Klutchko C, et al. (1987). "Structure of the gene for human beta 2-adrenergic receptor: expression and promoter characterization.". Proc. Natl. Acad. Sci. U.S.A. 84 (20): 6995–9. Bibcode 1987PNAS...84.6995E. doi:10.1073/pnas.84.20.6995. PMC 299215. PMID 2823249. //www.ncbi.nlm.nih.gov/pmc/articles/PMC299215/.
- Chung FZ, Wang CD, Potter PC, et al. (1988). "Site-directed mutagenesis and continuous expression of human beta-adrenergic receptors. Identification of a conserved aspartate residue involved in agonist binding and receptor activation.". J. Biol. Chem. 263 (9): 4052–5. PMID 2831218.
- Yang SD, Fong YL, Benovic JL, et al. (1988). "Dephosphorylation of the beta 2-adrenergic receptor and rhodopsin by latent phosphatase 2.". J. Biol. Chem. 263 (18): 8856–8. PMID 2837466.
- Kobilka BK, Dixon RA, Frielle T, et al. (1987). "cDNA for the human beta 2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor.". Proc. Natl. Acad. Sci. U.S.A. 84 (1): 46–50. Bibcode 1987PNAS...84...46K. doi:10.1073/pnas.84.1.46. PMC 304138. PMID 3025863. //www.ncbi.nlm.nih.gov/pmc/articles/PMC304138/.
- Chung FZ, Lentes KU, Gocayne J, et al. (1987). "Cloning and sequence analysis of the human brain beta-adrenergic receptor. Evolutionary relationship to rodent and avian beta-receptors and porcine muscarinic receptors.". FEBS Lett. 211 (2): 200–6. doi:10.1016/0014-5793(87)81436-9. PMID 3026848.
Cell surface receptor: G protein-coupled receptors
|
|
Class A:
Rhodopsin like |
|
|
Class B: Secretin like |
Orphan
|
- GPR (56
- 64
- 97
- 98
- 110
- 111
- 112
- 113
- 114
- 115
- 116
- 123
- 124
- 125
- 126
- 128
- 133
- 143
- 144
- 155
- 157)
|
|
Other
|
- Brain-specific angiogenesis inhibitor (1
- 2
- 3)
- Cadherin (1
- 2
- 3)
- Calcitonin
- CALCRL
- CD97
- Corticotropin-releasing hormone (1
- 2)
- EMR (1
- 2
- 3)
- Glucagon (GR
- GIPR
- GLP1R
- GLP2R)
- Growth hormone releasing hormone
- PACAPR1
- GPR
- Latrophilin (1
- 2
- 3
- ELTD1)
- Methuselah-like proteins
- Parathyroid hormone (1
- 2)
- Secretin
- Vasoactive intestinal peptide (1
- 2)
|
|
|
Class C: Metabotropic
glutamate / pheromone |
Taste
|
- TAS1R (1
- 2
- 3)
- TAS2R (1
- 3
- 4
- 5
- 7
- 8
- 9
- 10
- 13
- 14
- 16
- 19
- 20
- 30
- 31
- 38
- 39
- 40
- 41
- 42
- 43
- 45
- 46
- 50
- 60)
|
|
Other
|
- Calcium-sensing receptor
- GABA B (1
- 2)
- Glutamate receptor (Metabotropic glutamate (1
- 2
- 3
- 4
- 5
- 6
- 7
- 8))
- GPRC6A
- GPR (156
- 158
- 179)
- RAIG (1
- 2
- 3
- 4)
|
|
|
Class F:
Frizzled / Smoothened |
Frizzled
|
- Frizzled (1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10)
|
|
Smoothened
|
|
|
|
B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
|
|