| Structural highlights
Function
[ARTN_HUMAN] Ligand for the GFR-alpha-3-RET receptor complex but can also activate the GFR-alpha-1-RET receptor complex. Supports the survival of sensory and sympathetic peripheral neurons in culture and also supports the survival of dopaminergic neurons of the ventral mid-brain. Strong attractant of gut hematopoietic cells thus promoting the formation Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue.[1] [2] [GFRA3_HUMAN] Receptor for the glial cell line-derived neurotrophic factor, ARTN (artemin). Mediates the artemin-induced autophosphorylation and activation of the RET receptor tyrosine kinase.[3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Artemin (ARTN) is a member of the glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) which regulate the development and maintenance of many neuronal populations in the mammalian nervous system. Here we report the 1.92 A crystal structure of the complex formed between ARTN and its receptor GFRalpha3, which is the initiating step in the formation of a ternary signaling complex containing the shared RET receptor. It represents a new receptor-ligand interaction mode for the TGF-beta superfamily that reveals both conserved and specificity-determining anchor points for all GFL-GFRalpha pairs. In tandem with the complex structure, cellular studies using receptor chimeras implicate dyad-symmetric composite interfaces for recruitment and dimerization of RET, leading to intracellular signaling. These studies should facilitate the functional dissection of the specific versus pleiotropic roles of this system in neurobiology, as well as its exploitation for therapeutic applications.
Structure of artemin complexed with its receptor GFRalpha3: convergent recognition of glial cell line-derived neurotrophic factors.,Wang X, Baloh RH, Milbrandt J, Garcia KC Structure. 2006 Jun;14(6):1083-92. PMID:16765900[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Baloh RH, Tansey MG, Lampe PA, Fahrner TJ, Enomoto H, Simburger KS, Leitner ML, Araki T, Johnson EM Jr, 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. PMID:9883723
- ↑ Masure S, Geerts H, Cik M, Hoefnagel E, Van Den Kieboom G, Tuytelaars A, Harris S, Lesage AS, Leysen JE, Van Der Helm L, Verhasselt P, Yon J, Gordon RD. Enovin, a member of the glial cell-line-derived neurotrophic factor (GDNF) family with growth promoting activity on neuronal cells. Existence and tissue-specific expression of different splice variants. Eur J Biochem. 1999 Dec;266(3):892-902. PMID:10583383
- ↑ Baloh RH, Tansey MG, Lampe PA, Fahrner TJ, Enomoto H, Simburger KS, Leitner ML, Araki T, Johnson EM Jr, 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. PMID:9883723
- ↑ Wang X, Baloh RH, Milbrandt J, Garcia KC. Structure of artemin complexed with its receptor GFRalpha3: convergent recognition of glial cell line-derived neurotrophic factors. Structure. 2006 Jun;14(6):1083-92. PMID:16765900 doi:10.1016/j.str.2006.05.010
|
