RET signaling

Fleming MS, Vysochan A, Paixão S, Niu J, Klein R, Savitt JM, Luo W. Cis and trans RET signaling control the survival and central projection growth of rapidly adapting mechanoreceptors. Elife. 2015 Apr 02;4():e06828. PMID: 25838128; PMCID: PMC4408446.; Luo W, Enomoto H, Rice FL, Milbrandt J, Ginty DD. Molecular identification of rapidly adapting mechanoreceptors and their developmental dependence on ret signaling. Neuron. 2009 Dec 24;64(6):841–56. PMID: 20064391; PMCID: PMC2813518.; Luo W, Wickramasinghe SR, Savitt JM, Griffin JW, Dawson TM, Ginty DD. A hierarchical NGF signaling cascade controls Ret-dependent and Ret-independent events during development of nonpeptidergic DRG neurons. Neuron. 2007 Jun 07;54(5):739–54. doi: 10.1016/j.neuron.2007.04.027. PMID: 17553423.; Murakumo Y, Jijiwa M, Asai N, Ichihara M, Takahashi M. RET and neuroendocrine tumors. Pituitary. 2006;9(3):179–92. doi: 10.1007/s11102-006-0263-4. PMID: 17036197.; Kramer ER, Knott L, Su F, Dessaud E, Krull CE, Helmbacher F, Klein R. Cooperation between GDNF/Ret and ephrinA/EphA4 signals for motor-axon pathway selection in the limb. Neuron. 2006 Apr 06;50(1):35–47. doi: 10.1016/j.neuron.2006.02.020. PMID: 16600854.; Naughton CK, Jain S, Strickland AM, Gupta A, Milbrandt J. Glial cell-line derived neurotrophic factor-mediated RET signaling regulates spermatogonial stem cell fate. Biol Reprod. 2006 Feb;74(2):314–21. doi: 10.1095/biolreprod.105.047365. PMID: 16237148.; Ichihara M, Murakumo Y, Takahashi M. RET and neuroendocrine tumors. Cancer Lett. 2004 Feb 20;204(2):197–211. doi: 10.1016/s0304-3835(03)00456-7. PMID: 15013219.; Coulpier M, Anders J, Ibáñez CF. Coordinated activation of autophosphorylation sites in the RET receptor tyrosine kinase: importance of tyrosine 1062 for GDNF mediated neuronal differentiation and survival. J Biol Chem. 2002 Jan 18;277(3):1991–9. doi: 10.1074/jbc.m107992200. PMID: 11713247.; Enomoto H, Crawford PA, Gorodinsky A, Heuckeroth RO, Johnson EM, Milbrandt J. RET signaling is essential for migration, axonal growth and axon guidance of developing sympathetic neurons. Development. 2001 Oct;128(20):3963–74. doi: 10.1242/dev.128.20.3963. PMID: 11641220.; Paratcha G, Ledda F, Baars L, Coulpier M, Besset V, Anders J, Scott R, Ibáñez CF. Released GFRalpha1 potentiates downstream signaling, neuronal survival, and differentiation via a novel mechanism of recruitment of c-Ret to lipid rafts. Neuron. 2001 Jan;29(1):171–84. doi: 10.1016/s0896-6273(01)00188-x. PMID: 11182089.; Masure S, Cik M, Hoefnagel E, Nosrat CA, Van der Linden I, Scott R, Van Gompel P, Lesage AS, Verhasselt P, Ibáñez CF, Gordon RD. Mammalian GFRalpha -4, a divergent member of the GFRalpha family of coreceptors for glial cell line-derived neurotrophic factor family ligands, is a receptor for the neurotrophic factor persephin. J Biol Chem. 2000 Dec 15;275(50):39427–34. doi: 10.1074/jbc.m003867200. PMID: 10958791.; Tansey MG, Baloh RH, Milbrandt J, Johnson EM. GFRalpha-mediated localization of RET to lipid rafts is required for effective downstream signaling, differentiation, and neuronal survival. Neuron. 2000 Mar;25(3):611–23. doi: 10.1016/s0896-6273(00)81064-8. PMID: 10774729.; Baloh RH, Tansey MG, Lampe PA, Fahrner TJ, Enomoto H, Simburger KS, Leitner ML, Araki T, Johnson EM, Milbrandt J. Artemin, a novel member of the GDNF ligand family, supports peripheral and central neurons and signals through the GFRalpha3-RET receptor complex. Neuron. 1998 Dec;21(6):1291–302. doi: 10.1016/s0896-6273(00)80649-2. PMID: 9883723.; Milbrandt J, de Sauvage FJ, Fahrner TJ, Baloh RH, Leitner ML, Tansey MG, Lampe PA, Heuckeroth RO, Kotzbauer PT, Simburger KS, Golden JP, Davies JA, Vejsada R, Kato AC, Hynes M, Sherman D, Nishimura M, Wang L, Vandlen R, Moffat B, Klein RD, Poulsen K, Gray C, Garces A, Henderson CE, Phillips HS, Johnson EM. Persephin, a Novel Neurotrophic Factor Related to GDNF and Neurturin. Neuron. 1998 Feb;20(2):245–53. doi: 10.1016/s0896-6273(00)80453-5.; Jing S, Yu Y, Fang M, Hu Z, Holst PL, Boone T, Delaney J, Schultz H, Zhou R, Fox GM. GFRalpha-2 and GFRalpha-3 are two new receptors for ligands of the GDNF family. J Biol Chem. 1997 Dec 26;272(52):33111–7. doi: 10.1074/jbc.272.52.33111. PMID: 9407096.; Creedon DJ, Tansey MG, Baloh RH, Osborne PA, Lampe PA, Fahrner TJ, Heuckeroth RO, Milbrandt J, Johnson EM. Neurturin shares receptors and signal transduction pathways with glial cell line-derived neurotrophic factor in sympathetic neurons. Proc. Natl. Acad. Sci. U.S.A. 1997 Jun 24;94(13):7018–23. doi: 10.1073/pnas.94.13.7018.; Baloh RH, Tansey MG, Golden JP, Creedon DJ, Heuckeroth RO, Keck CL, Zimonjic DB, Popescu NC, Johnson EM, Milbrandt J. TrnR2, a novel receptor that mediates neurturin and GDNF signaling through Ret. Neuron. 1997 May;18(5):793–802. doi: 10.1016/s0896-6273(00)80318-9. PMID: 9182803.; Kotzbauer PT, Lampe PA, Heuckeroth RO, Golden JP, Creedon DJ, Johnson EM, Milbrandt J. Neurturin, a relative of glial-cell-line-derived neurotrophic factor. Nature. 1996 Dec 05;384(6608):467–70. doi: 10.1038/384467a0. PMID: 8945474.; Treanor JJ, Goodman L, de Sauvage F, Stone DM, Poulsen KT, Beck CD, Gray C, Armanini MP, Pollock RA, Hefti F, Phillips HS, Goddard A, Moore MW, Buj-Bello A, Davies AM, Asai N, Takahashi M, Vandlen R, Henderson CE, Rosenthal A. Characterization of a multicomponent receptor for GDNF. Nature. 1996 Jul 04;382(6586):80–3. doi: 10.1038/382080a0. PMID: 8657309.; Jing S, Wen D, Yu Y, Holst PL, Luo Y, Fang M, Tamir R, Antonio L, Hu Z, Cupples R, Louis JC, Hu S, Altrock BW, Fox GM. GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF. Cell. 1996 Jun 28;85(7):1113–24. doi: 10.1016/s0092-8674(00)81311-2. PMID: 8674117.; Carlson KM, Dou S, Chi D, Scavarda N, Toshima K, Jackson CE, Wells SA, Goodfellow PJ, Donis-Keller H. Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B. Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1579–83. PMID: 7906417; PMCID: PMC43203.; Hofstra RMW, Landsvater RM, Ceccherini I, Stulp RP, Stelwagen T, Luo Y, Pasini B, Hoppener JWM, van Amstel HKP, Romeo G, Lips CJM, Buys CHCM. A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma. Nature. 1994 Jan;367(6461):375–6. doi: 10.1038/367375a0.; Romeo G, Ronchetto P, Luo Y, Barone V, Seri M, Ceccherini I, Pasini B, Bocciardi R, Lerone M, Kääriäinen H. Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung's disease. Nature. 1994 Jan 27;367(6461):377–8. doi: 10.1038/367377a0. PMID: 8114938.; Edery P, Lyonnet S, Mulligan LM, Pelet A, Dow E, Abel L, Holder S, Nihoul-Fékété C, Ponder BA, Munnich A. Mutations of the RET proto-oncogene in Hirschsprung's disease. Nature. 1994 Jan 27;367(6461):378–80. doi: 10.1038/367378a0. PMID: 8114939.; Schuchardt A, D'Agati V, Larsson-Blomberg L, Costantini F, Pachnis V. Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature. 1994 Jan 27;367(6461):380–3. doi: 10.1038/367380a0. PMID: 8114940.; Mulligan LM, Kwok JBJ, Healey CS, Elsdon MJ, Eng C, Gardner E, Love DR, Mole SE, Moore JK, Papi L, Ponder MA, Telenius H, Tunnacliffe A, Ponder BAJ. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature. 1993 Jun;363(6428):458–60. doi: 10.1038/363458a0.; Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science. 1993 May 21;260(5111):1130–2. doi: 10.1126/science.8493557. PMID: 8493557.; Grieco M, Santoro M, Berlingieri MT, Melillo RM, Donghi R, Bongarzone I, Pierotti MA, Della Porta G, Fusco A, Vecchio G. PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas. Cell. 1990 Feb 23;60(4):557–63. doi: 10.1016/0092-8674(90)90659-3. PMID: 2406025.; Takahashi M, Buma Y, Iwamoto T, Inaguma Y, Ikeda H, Hiai H. Cloning and expression of the ret proto-oncogene encoding a tyrosine kinase with two potential transmembrane domains. Oncogene. 1988 Nov;3(5):571–8. PMID: 3078962.

Metabolites

ATP(4-)

Formula: C10H12N5O13P3 (502.9644492)

CAS ID:

ADP(3-)

Formula: C10H12N5O10P2 (424.0059412)

CAS ID:



Enzyme

EC Number name full name note
2.7.1.137 phosphatidylinositol 3-kinase ATP:1-phosphatidyl-1D-myo-inositol 3-phosphotransferase
2.7.1.153 phosphatidylinositol-4,5-bisphosphate 3-kinase ATP:1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate 3-phosphotransferase
2.7.10.1 receptor protein-tyrosine kinase ATP:[protein]-L-tyrosine O-phosphotransferase (receptor-type)
2.7.11.1 non-specific serine/threonine protein kinase ATP:protein phosphotransferase (non-specific)
3.1.3.48 protein-tyrosine-phosphatase protein-tyrosine-phosphate phosphohydrolase
3.1.4.11 phosphoinositide phospholipase C 1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate inositoltrisphosphohydrolase


Proteins

Protein ID name full name