Recommendations for Nomenclature of the Insulin-Like Growth Factor Binding Protein Superfamily
R. C. Baxter,
M. A. Binoux,
D. R. Clemmons,
C. A. Conover,
S. L. S. Drop,
J. M. P. Holly,
S. Mohan,
Y. Oh and
R. G. Rosenfeld
Kolling Institute of Medical Research (R.C.B.), St.
Leonards, New South Wales 2065, Australia; INSERM U-142, Hopital
Sainte-Antoine (M.A.B.), Paris, France; Department of Medicine,
Division of Endocrinology, University of North Carolina School of
Medicine (D.R.C.), Chapel Hill, North Carolina 27599-7170; Endocrine
Research Unit, Mayo Clinic (C.A.C.), Rochester, Minnesota 55905-0001;
Division of Endocrinology, Sophia Childrens Hospital (S.L.S.D.),
Rotterdam, Netherlands; Department of Surgery, Bristol Royal Infirmary
(J.M.P.H.) Bristol, United Kingdom; Department of Medicine, Loma Linda
University (S.M.) Loma Linda, California 92357-0001; Department of
Pediatrics, Oregon Health Sciences University (Y.O., R.G.R.) Portland,
Oregon 97201
Address correspondence and requests for reprints to: Ron G. Rosenfeld, M.D., Department of Pediatrics, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97201. E-mail: rosenfer{at}ohsu.edu
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Introduction
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THE NOMENCLATURE for the
insulin-like growth factor (IGF) binding proteins (IGFBP) was
established at the 2nd and 3rd International IGF Symposia (1, 2). The IGFBPs constitute a family of six structurally
related proteins that bind IGF peptides with high affinity (typical
Kd in the 10-10 to 10-11
M range). They share an overall protein sequence
identity of approximately 50% and contain 1618 conserved cysteines
in the NH2- and COOH-terminal regions (3). Recently, the
predicted protein product of the mac25 complementary DNA (4) was shown
to be structurally related to the IGFBPs, especially in the
amino-terminal region, where 1112 of the 12 cysteines found in IGFBPs
16 are conserved (5). The protein was synthesized in a baculovirus
expression system (5), found to be identical to previously described
tumor-derived adhesion factor (6) and prostacyclin-stimulating factor
(7), and to bind IGF-I, IGF-II, and insulin, but with relatively low
affinity. It was, accordingly, provisionally named IGFBP-7 (5, 8).
A closely related family of genes (CCN) has been identified,
encoding immediate early gene products, connective tissue growth
factor, and cyr61, as well as a putative avian
proto-oncogene, nov (CCN stands for connective tissue growth
factor, Cyr61/Cef10, nephroblastoma overexpressed gene) (9). The
amino-terminal regions of the predicted proteins are structurally
homologous to the classical IGFBPs, with conservation of the
cysteine-rich region. As is the case with mac25/TAF/PSF/IGFBP-7, the
carboxyl terminus of IGFBPs 16 is not conserved in these three
proteins. The protein product of the CTGF gene has been synthesized in
a baculovirus system and has been found to bind IGF-I and IGF-II with
low affinity (10). This protein was provisionally named IGFBP-8, and,
on the basis of their structural homologies, the protein products of
nov and cyr61 were provisionally named IGFBP-9
and IGFBP-10, respectively (10).
The structural relationship of these proteins, especially in
the amino-terminal regions is clear and suggests that the classical six
IGFBPs and these low-affinity IGF binders are members of an IGFBP
superfamily. This superfamily consists of at least three gene families:
1) the IGFBPs, 2) the protein product of the mac25 gene, and 3) members
of the CCN family. In light of their relatively low affinities for IGF
peptides, it is recommended that they not be named IGF binding
proteins, but, rather, be termed insulin-like growth factor binding
protein-related proteins (IGFBP-rP), until further elucidation of their
molecular, biochemical, and physiological relationships to the
classical IGFBPs (see Table 1
).
Received March 20, 1998.
Revised May 7, 1998.
Accepted May 19, 1998.
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References
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