| Literature References | 1. AIRAKSINEN, M., TITIEVSKY, A. AND SAARMA, S.
GDNF family neurotrophic factor signalling: four masters, one servant?
MOL.CELL.NEUROSCIENCE 13 313-325 (1999).
2. CREEDON, D., TANSEY, M., BALOH, R., OSBORNE, P., LAMPE, P., FAHRNER,
T., HEUCKEROTH, R., MILBRANDT, J. AND JOHNSON, E.
Neurturin shares receptors and signal transduction pathways with glial cell
line-derived neurotrophic factor in sympathetic neurons.
PROC.NATL.ACAD.SCI.U.S.A. 94 7018-7023 (1997).
3. BALOH, R., GORODINSKY, A., GOLDEN, J., TANSEY, M., KECK, C., POPESCU,
N., JOHNSON, E. AND MILBRANDT, J.
GFRalpha3 is an orphan member of the GDNF/neurturin/persephin receptor
family.
PROC.NATL.ACAD.SCI.U.S.A. 95 5801-5806 (1998).
4. THOMPSON, J., DOXAKIS, E., PINON, L., STRACHAN, P., BUJ-BELLO, A.,
WYATT, S., BUCHMAN, V. AND DAVIES, A.
GFRalpha-4, a new GDNF family receptor.
MOL.CELL.NEUROSCIENCE 11 117-126 (1998).
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| Documentation | Glial cell line-derived neurotrophic factor (GDNF) and its related factors
neurturin (NTN), artemin (ART) and persephin (PSP), are members of the GDNF
family of neurotrophic factors. They form a sub-group in the transforming
growth factor-beta (TGF-beta) superfamily. These factors are involved in
the promotion of neurone survival, exerting their effects through specific
receptors.
The GDNF family receptors (GFRs) are glycosyl-phosphatidylinositol-linked,
cell surface receptors [1]. Four receptor subtypes, termed GFRalpha-1 to 4,
are currently recognised. GFRalpha-1 and 2 are activated by GDNF and NTN
respectively, although some degree of ligand promiscuity is thought to
occur [2]. Homologues for these receptor subtypes have been cloned from
mammalian and avian tissue. The principal ligand for GFRalpha-3 is artemin.
This receptor subtype is currently described only in mammals [3]. GFRalpha-4
is activated by persephin and has so far only been found in chicken [4].
Activation of GFR family members triggers their interaction with the
membrane-bound receptor kinase Ret. This induces Ret homo-dimerisation,
triggering a cascade of intracellular signalling events such as the
activation of the Ras-mitogen-activated protein kinase (MAPK),
phosphpinositol-3-kinase (PI3K), Jun N-terminal kinase (JNK) and
phospholipase C gamma (PLC gamma) dependent pathways [1].
GDNFRECEPTOR is a 6-element fingerprint that provides a signature for the
GDNF receptor family. The fingerprint was derived from an initial alignment
of 9 sequences: the motifs were drawn from conserved regions spanning
virtually the full alignment length - motif 1 lies at the end of the first
globular cysteine-rich domain; motif 2 spans a putative alpha-helix in the
second globular domain; motifs 3 and 6 lie at the end of the second and
third globular domains respectively; and motifs 4 and 5 are of unknown
function. Two iterations on SPTR37_10f were required to reach convergence,
at which point a true set comprising 20 sequences was identified. Two
partial matches were also found, Q9Z2A2 and Q9Z2A3, which are splice
variants of the Mus musculus GFRalpha-2 lacking a portion of the N-terminal
section of the receptor.
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