| Literature References | 1. ATTWOOD, T.K. AND FINDLAY, J.B.C.
Fingerprinting G protein-coupled receptors.
PROTEIN ENG. 7(2) 195-203 (1994).
2. ISHIHARA T., NAKAMURA S., KAZIRO, Y., TAKAHASHI, T., TAKAHASHI, K.
AND NAGATA, S.
Molecular cloning and expression of a cDNA encoding the secretin receptor
EMBO J. 10 1635-1641 (1991).
3. LIN, H.Y., HARRIS, T.L., FLANNERY, M.S., ARUFFO, A., KAJI, E.H.,
GORN, A., KOLAKOWSKI, L.F., LODISH, H.F. AND GOLDRING, S.R.
Expression cloning of adenylate cyclase-coupled calcitonin receptor
SCIENCE 254 1022-1024 (1991).
4. JUEPPNER, H., ABOU-SAMRA, A.-B., FREEMAN, M., KONG, X.F.,
SCHIPANI, E., RICHARDS, J., KOLALOWSKI, L.F., HOCK, J., POTTS, J.T.,
KRONENBERG, H.M. AND SEGRE, G.E.
A G protein linked receptor for parathyroid hormone and parathyroid
hormone-related peptide.
SCIENCE 254 1024-1026 (1991).
5. ISHIHARA, T., SHIGEMOTO, R., MORI, K., TAKAHASHI, K. AND NAGATA, S.
Functional expression and tissue distribution of a novel receptor for
vasoactive intestinal polypeptide.
NEURON 8(4) 811-819 (1992).
6. HSIUNG, H.M., SMITH, D.P., ZHANG, X.Y., BENNETT, T., ROSTECK, P.R.
AND LAI, M.H.
Structure and functional expression of a complementary DNA for porcine
growth hormone-releasing hormone receptor.
NEUROPEPTIDES 25 1-10 (1993).
7. GAYLINN, B.D., HARRISON, J.K., ZYSK, J.R., LYONS, C.E., LYNCH, K.R.
AND THORNER, M.O.
Molecular cloning and expression of a human anterior pituitary receptor for growth
hormone-releasing hormone.
MOL.ENDOCRINOL. 7 77-84 (1993).
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| Documentation | G protein-coupled receptors (GPCRs) constitute a vast protein family that
encompasses a wide range of functions (including various autocrine, para-
crine and endocrine processes). They show considerable diversity at the
sequence level, on the basis of which they can be separated into distinct
groups. We use the term clan to describe the GPCRs, as they embrace a group
of families for which there are indications of evolutionary relationship,
but between which there is no statistically significant similarity in
sequence [1]. The currently known clan members include the rhodopsin-like
GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating
pheromone receptors, and the metabotropic glutamate receptor family.
The secretin-like GPCRs include secretin [2], calcitonin [3], parathyroid
hormone/parathyroid hormone-related peptides [4] and vasoactive intestinal
peptide [5], all of which activate adenylyl cyclase and the phosphatidyl-
inositol-calcium pathway. The amino acid sequences of the receptors contain
high proportions of hydrophobic residues grouped into 7 domains, in a
manner reminiscent of the rhodopsins and other receptors believed to inter-
act with G proteins. However, while a similar 3D framework has been
proposed to account for this, there is no significant sequence similarity
between these families: the secretin-like receptors thus bear their own
unique `7TM' signature.
Growth hormone (GH)-releasing hormone (GHRH) belongs to the family of gut-
neuropeptide hormones that includes glucagon, secretin and vasoactive
intestinal peptide (VIP) [6]. The receptors for this peptide family involve
similar signal transduction pathways - on hormone binding, they interact
with G protein `Gs' and cause stimulation of adenylate cyclase [6]. Acting
through the GHRH receptor (GHRHR), GH plays a pivotal role in the regulation
of GH synthesis and secretion in the pituitary, possibly serving other roles
in different tissues [6]. The human pituitary GHRHR is a 423-amino acid
protein that has the characteristic 7TM signature of the secretin-like GPCR
superfamily, sharing 47%, 42%, 35%, and 28% identity with receptors for
VIP, secretin, calcitonin and PTH, respectively [7].
GHRHRECEPTOR is a 9-element fingerprint that provides a signature for the
growth hormone-releasing hormone receptors. The fingerprint was derived
from an initial alignment of 3 sequences: the motifs were drawn from
conserved regions spanning the full alignment length, focusing on those
sections that characterise the GHRH receptors but distinguish them from the
rest of the secretin-like GPCR superfamily - motifs 1-5 span the N-terminal
putative extracellular domain; motif 6 spans the second cytoplasmic loop,
leading into the fourth TM domain; motif 7 lies in the third cytoplasmic
loop; and motifs 8 and 9 reside in the cytoplasmic C-terminus. Two
iterations on SPTR37_10f were required to reach convergence, at which point
a true set comprising 4 sequences was identified.
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