A second human calcitonin/CGRP gene

Abstract

The calcitonin (CT) gene is alternatively expressed in a tissue-specific fashion producing either the calcium regulatory hormone CT in the thyroid or the neuropeptide calcitonin gene related peptide (CGRP) in the brain. In medullary carcinoma of the thyroid both peptides are produced. We present here evidence for the existence in the human genome of a second CT gene, which is also expressed in human medullary thyroid carcinoma. This gene encodes a second human CGRP, differing from the known human CGRP in 3 of the 37 amino acids.

Human alpha‐calcitonin gene‐related peptide (CGRP) is a potent vasodilator in human mesenteric vasculature.

“…A second P-CGRP gene is now known to be present also (Rosenfeld et al, 1984). In man, like the rat, two CGRP peptides have been predicted using gene cloning (Edbrooke et al, 1985;Jonas et al, 1985;Steenbergh et al, 1984Steenbergh et al, , 1985 and one, human a-CGRP, has been isolated from human medullary thyroid carcinoma tissue (Morris et al, 1984). Immunocytochemical analysis has localised CGRP in the rat in discrete regions of the central nervous system (Skofitsch & Jacobowitz, 1985a, b) and at nerve endings within the vasculature and heart (Mulderry et al, 1985;Sigrist et al, 1986).…”

A third human CALC (pseudo)gene on chromosome 11

“…The possibility that this gene encodes a CT-or CGRP-Iike polypeptide was not ruled out. As shown in figs 1 and 2, a genomic 3.2 kb TaqI fragment (previously termed 3.0 kb in [8,20]) was identified which hybridized to probes containing exon 2 and/or exon 3 sequences of the CALC-I gene or the CALC-II gene, but which does not belong to either one of these two genes. The 8.0 kb and 6.5 kb fragments in fig.1 are the two alleles of a CALC-I gene-specific restriction fragment length polymorphism for TaqI [21] and the 2.3 kb TaqI fragment is derived from the CALC-II gene [6].…”

“…CGRP-encoding exon 5 sequences start another 1.2 kb further downstream in both of these genes [3,6]. Nucleotide sequence analysis of a region of approx.…”

“…H6ppener, Institute of Molecular Biology, State University of Utrecht, Padualaan 8, 3584 CH Utrecht, The Netherlands [3,4]. In medullary thyroid carcinoma (MTC; a tumour of the CT-producing thyroidal C-cells), both CT mRNA and CGRP mRNA are produced from the human CT/CGRP gene (or 'CALC-I gene', [5]).…”

Demonstration of the neurotransmitter role of calcitonin gene‐related peptides (CGRP) by immunoblockade with anti‐CGRP monoclonal antibodies

“…A second CGRP gene encoding another 37-amino acid peptide was subsequently identified (Amara et al, 1985;Steenbergh et al, 1985). This peptide (PCGRP) differs from the originally discovered CGRP (aCGRP) by only one amino acid at position 35 in the rat.…”