| Literature References | 1. STEWART, C. AND ROTWEIN, P.
Growth, differentiation and survival: multiple physiological functions for
insulin-like growth factors.
PHYSIOL.REV. 76 1005-1026 (1996).
2. HWA, V., OH, Y. AND ROSENFELD, R.
The Insulin-Like Growth Factor-Binding Protein (IGFBP) Superfamily.
ENDOCR.REV. 20 761-787 (1999).
3. OH, Y., MULLER. H., PHAM, H. AND ROSENFELD, R.
Demonstration of receptors for insulin-like growth factor binding
protein-3 on Hs578T human breast cancer cells.
J.BIOL.CHEM. 268 26045-26048 (1993).
4. ANDRESS, D.
Heparin modulates the binding of insulin-like growth factor (IGF) binding
protein-5 to a membrane protein in osteoblastic cells.
J.BIOL.CHEM. 270 28289-28296 (1995).
5. MOHAN, S., NAKAO, Y., HONDA, Y., LANDALE, E., LESSER, U., DONY, C.,
LANG, K. AND BAYLINK, D.
Studies on the mechanisms by which insulin-like growth factor (IGF) binding
protein-4 (IGFBP-4) and IGFBP-5 modulate IGF actions in bone cells.
J.BIOL.CHEM.270 20424-20431 (1995).
6. RAJAH, R., VALENTINIS, B. AND COHEN, P.
Insulin-like growth factor (IGF)-binding protein-3 induces apoptosis and
mediates the effects of transforming growth factor-beta1 on programmed cell
death through a p53- and IGF-independent mechanism.
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7. FROMMER K., REICHENMILLER, K., SCHUTT, B., HOEFLICH, A., RANKE, M.,
DODT, G. AND ELMLINGER, M.
IGF-independent effects of IGFBP-2 on the human breast cancer cell line
Hs578T.
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8. BUSUND, L., RICHARDSEN, E., BUSUND, R., UKKONEN, T., BJORNSEN, T.,
BUSCH, C. AND STALSBERG, H.
Significant expression of IGFBP2 in breast cancer compared with benign
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| Documentation | Insulin-like growth factors (IGFs)-I and -II are small secreted peptides
that stimulate the survival, and promote the proliferation and
differentiation, of many cell types [1]. In biological fluids, these growth
factors are usually bound to IGF binding proteins (IGFBPs), which regulate
their availability and activity by prolonging their half-life and
modulating their receptor interactions.
To date, six IGFBP family members have been identified (termed IGFBP1-6)
[2]. They share a conserved gene (intron-exon) organisation and high IGF
binding affinity. Structurally, the proteins also share a common domain
architecture, possessing a conserved N-terminal IGFBP domain, a highly
variable mid-section, and a thyroglobulin type-1 (Tg1) domain in their
C-terminal regions.
In addition to their role in the regulation of IGF activity, there is
evidence for the direct association of IGFBPs with a variety of
extracellular and cell surface molecules [3,4], with consequent effects
upon important biological processes. These include modulation of bone cell
proliferation [5], and growth arrest of breast and prostate cancer cells
[3,6].
IGFBP2 is involved in a variety of biological processes, including the
regulation of cell adhesion, migration and proliferation [7]. The protein
is overexpressed in a number of carcinomas [8,9], and increased IGFBP2
concentrations have been described in serum and cyst fluids surrounding
tumours of different histologies, such as lung tumours, prostate cancer and
brain tumours [10]. Consequently, IGFBP2 may represent a valuable marker
for tumour diagnosis and surveillance.
IGFBPFAMILY2 is a 3-element fingerprint that provides a signature for
insulin-like growth factor-binding protein 2. The fingerprint was derived
from an initial alignment of 9 sequences: the motifs were drawn from
conserved regions in the N- and C-terminal thirds of the alignment,
focusing on those sections that characterise IGFBP2 but distinguish it from
other family members - motif 1 resides within the IGFBP domain; motif
2 lies partially within the Tg1 domain; and motif 3 resides wholly within
the Tg1 domain. Two iterations on SPTR57_40f were required to reach
convergence, at which point a true set comprising 16 sequences was
identified. A single partial match was also found, Q9D057_MOUSE, a
mouse sequence that fails to match motif 1.
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