and ~3 with 37 kDa); these agree in 81-90 % of
their amino acid sequences [120]. The ~ chains of
Drosophila and Caenorhabditis have 80-85 %
sequence agreement with those of the mammals
[226, 241]. ~ chains form stable complexes with
y chains (8-10 kDa). Just how many different
y chains there are is not yet clear, but they are
more or less tissue specific and the six known
sequences agree by up to 55 % [62, 203, 217].
8.9.2 Nicotinic Acetylcholine Receptors
The nicotinic acetylcholine receptor (nAchR)
from vertebrate muscle or the electric organ of
the electric ray Torpedo californica is constructed
of five polypeptide chains according to the formula a2~Y()' and these are organized symmetrically around a central channel. Each subunit carries between one and four N-linked carbohydrate
chains. The four subunits within anyone species
are about 35-50 % homologous. In mammals
(the rat and cattle), but not in the chicken, the
y subunit in adult animals is replaced by an E subunit encoded by its own gene [235]. Torpedo, the
chicken and all mammals that have been examined possess only one a gene, whereas Xenopus laevis has two genes which are expressed
simultaneously [76]. nAChRs are also found in
the CNS, where they apparently show great
diversity: a whole series of nAChR subunits have
been identified via their cDNAs in the rat,
chicken and goldfish; for example, in the rat
there are a2, a3, a4, a5, ~2, ~3 and na2 (= ~4).
The a sequences (a1-a5) show 49-55 %
sequence similarity and the ~ sequences (~1-~3)
show 43-64 % [21]. Three a subunits have been
sequenced via their cDNAs in Drosophila melanogaster and one has been identified in the locust
Schistocerca migratoria [132, 191].
8.9.3 Insulin Receptors
The mammalian insulin receptor consists of four
glycosylated polypeptide chains, linked by disulphide bridges, according to the formula (a~)z.
The exclusively extracellular a subunits (125135 kDa) make up the insulin-binding site; the
~ subunits (90-95 kDa) are organized into an
extracellular domain associated with the a subunits, a membrane segment of about 23 nonpolar amino acids, and a cytoplasmic domain with
tyrosine kinase activity. Binding of a ligand
results initially in the self-phosphorylation of the
References
311
chain, which in its activated form phosphorylates
other proteins and sets in motion a cascade leading to the metabolic effects of insulin. The a and
~ subunits are produced from the same precursor
of about 200 kDa. Insulin receptors are present in
various very different cell types from the bony
fish to man. They remain very similar in binding
affinity and specificity, despite the reduced immunological similarity associated with increasing
evolutionary distance [199, 212].
The IGF-I receptor has the same basic structure as the insulin receptor and is homologous in
its subunit sequence. It also binds IGF-II but
more weakly than IGF-1. The specific membrane
protein identified previously as the IGF-II receptor has a structure very different to that of the
insulin and IGF-I receptors; it consists of a single
polypeptide of 2450 amino acids which shows
80 % sequence agreement with the mannose-6phosphate receptor of the lysosomes and it therefore belongs to a completely different receptor
family [145]. This receptor is unlikely to be
responsible for the physiological effects of IGF-II
and it may well be that a specific IGF-II receptor
awaits discovery.
References
1. Acher, R. and Chauvet J.: Structure, processing and
evolution of the neuro-hypophysical hormoneneurophysin precursors. Biochimie 70: 1197-1207
(1988)
2. Andersen A. C. et aI.: Immunohistological detection of
methionin-enkephalin-like and endorphin-like material
in the digestive tract and in the nervous system of the
mussel, Mytilus edulis L. Gen. compo Endocrinoi. 62:
111-119 (1986)
3. Andrews P. C. and Ronner P.: Isolation and structures
of glucagon and glucagonlike peptide from catfish pancreas. J. bioI. Chern. 260: 3910-14 (1985)
4. Andrews P. C. et al.: Isolation and characterization of a
variant somatostatin-14 and two related somatostatins
of 34 and 37 residues from lamprey (Petromyzon marinus). J. BioI. Chern. 263: 15809-14 (1988)
5. Attwood T. K., Eliopoulos E. E. and Findlay J. P. C.:
Multiple sequence alignment of protein families showing
low sequence homology. A methodological approach
using data-base pattern-matching discriminators for Gprotein-linked receptors. Gene 98: 153-159 (1991)
6. Bajaj M. et aI.: Coypu insulin. Primary structure, conformation and biological properties of a hystricomorph
rodent insulin. Biochem. J. 238: 345-351 (1986)
7. Balasubramaniam A. et aI.: Detection of conformational isomers of anglerfish peptide YG (aPY) by
reversed phase chromatography. Int. J. Peptide Prot.
Res. 34: 158-160 (1989)
8. Beebe D. C. et aI.: Lentropin, a protein that controls
lens fiber formation, is related functionally and immu-
their amino acid sequences [120]. The ~ chains of
Drosophila and Caenorhabditis have 80-85 %
sequence agreement with those of the mammals
[226, 241]. ~ chains form stable complexes with
y chains (8-10 kDa). Just how many different
y chains there are is not yet clear, but they are
more or less tissue specific and the six known
sequences agree by up to 55 % [62, 203, 217].
8.9.2 Nicotinic Acetylcholine Receptors
The nicotinic acetylcholine receptor (nAchR)
from vertebrate muscle or the electric organ of
the electric ray Torpedo californica is constructed
of five polypeptide chains according to the formula a2~Y()' and these are organized symmetrically around a central channel. Each subunit carries between one and four N-linked carbohydrate
chains. The four subunits within anyone species
are about 35-50 % homologous. In mammals
(the rat and cattle), but not in the chicken, the
y subunit in adult animals is replaced by an E subunit encoded by its own gene [235]. Torpedo, the
chicken and all mammals that have been examined possess only one a gene, whereas Xenopus laevis has two genes which are expressed
simultaneously [76]. nAChRs are also found in
the CNS, where they apparently show great
diversity: a whole series of nAChR subunits have
been identified via their cDNAs in the rat,
chicken and goldfish; for example, in the rat
there are a2, a3, a4, a5, ~2, ~3 and na2 (= ~4).
The a sequences (a1-a5) show 49-55 %
sequence similarity and the ~ sequences (~1-~3)
show 43-64 % [21]. Three a subunits have been
sequenced via their cDNAs in Drosophila melanogaster and one has been identified in the locust
Schistocerca migratoria [132, 191].
8.9.3 Insulin Receptors
The mammalian insulin receptor consists of four
glycosylated polypeptide chains, linked by disulphide bridges, according to the formula (a~)z.
The exclusively extracellular a subunits (125135 kDa) make up the insulin-binding site; the
~ subunits (90-95 kDa) are organized into an
extracellular domain associated with the a subunits, a membrane segment of about 23 nonpolar amino acids, and a cytoplasmic domain with
tyrosine kinase activity. Binding of a ligand
results initially in the self-phosphorylation of the
References
311
chain, which in its activated form phosphorylates
other proteins and sets in motion a cascade leading to the metabolic effects of insulin. The a and
~ subunits are produced from the same precursor
of about 200 kDa. Insulin receptors are present in
various very different cell types from the bony
fish to man. They remain very similar in binding
affinity and specificity, despite the reduced immunological similarity associated with increasing
evolutionary distance [199, 212].
The IGF-I receptor has the same basic structure as the insulin receptor and is homologous in
its subunit sequence. It also binds IGF-II but
more weakly than IGF-1. The specific membrane
protein identified previously as the IGF-II receptor has a structure very different to that of the
insulin and IGF-I receptors; it consists of a single
polypeptide of 2450 amino acids which shows
80 % sequence agreement with the mannose-6phosphate receptor of the lysosomes and it therefore belongs to a completely different receptor
family [145]. This receptor is unlikely to be
responsible for the physiological effects of IGF-II
and it may well be that a specific IGF-II receptor
awaits discovery.
References
1. Acher, R. and Chauvet J.: Structure, processing and
evolution of the neuro-hypophysical hormoneneurophysin precursors. Biochimie 70: 1197-1207
(1988)
2. Andersen A. C. et aI.: Immunohistological detection of
methionin-enkephalin-like and endorphin-like material
in the digestive tract and in the nervous system of the
mussel, Mytilus edulis L. Gen. compo Endocrinoi. 62:
111-119 (1986)
3. Andrews P. C. and Ronner P.: Isolation and structures
of glucagon and glucagonlike peptide from catfish pancreas. J. bioI. Chern. 260: 3910-14 (1985)
4. Andrews P. C. et al.: Isolation and characterization of a
variant somatostatin-14 and two related somatostatins
of 34 and 37 residues from lamprey (Petromyzon marinus). J. BioI. Chern. 263: 15809-14 (1988)
5. Attwood T. K., Eliopoulos E. E. and Findlay J. P. C.:
Multiple sequence alignment of protein families showing
low sequence homology. A methodological approach
using data-base pattern-matching discriminators for Gprotein-linked receptors. Gene 98: 153-159 (1991)
6. Bajaj M. et aI.: Coypu insulin. Primary structure, conformation and biological properties of a hystricomorph
rodent insulin. Biochem. J. 238: 345-351 (1986)
7. Balasubramaniam A. et aI.: Detection of conformational isomers of anglerfish peptide YG (aPY) by
reversed phase chromatography. Int. J. Peptide Prot.
Res. 34: 158-160 (1989)
8. Beebe D. C. et aI.: Lentropin, a protein that controls
lens fiber formation, is related functionally and immu-