◀ Back to IGF1
IGF1 — IGFBP6
Pathways - manually collected, often from reviews:
-
Reactome Reaction:
IGF1
→
IGFBP6
(direct_complex)
Marinaro et al., Eur J Biochem 2000*, Mohan et al., J Endocrinol 2002, Firth et al., Endocr Rev 2002, Headey et al., Mol Endocrinol 2004*, Headey et al., J Mol Endocrinol 2004*, Holly et al., Neuroendocrinology 2006, Bach et al., Endocrinology 1994*, Bach et al., J Biol Chem 1993, Cianfarani et al., Experientia 1993, Bach et al., Biochim Biophys Acta 1996
-
Reactome Reaction:
IGF1
→
IGFBP6
(reaction)
Marinaro et al., Eur J Biochem 2000*, Mohan et al., J Endocrinol 2002, Firth et al., Endocr Rev 2002, Headey et al., Mol Endocrinol 2004*, Headey et al., J Mol Endocrinol 2004*, Holly et al., Neuroendocrinology 2006, Bach et al., Endocrinology 1994*, Bach et al., J Biol Chem 1993, Cianfarani et al., Experientia 1993, Bach et al., Biochim Biophys Acta 1996
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
Text-mined interactions from Literome
Spicer et al., Domest Anim Endocrinol 1999
:
In a third series of experiments,
IGFBP-3 inhibited
125I-IGF-I binding to granulosa cells
Fottner et al., Horm Metab Res 1999
:
In the present study, we therefore characterized the IGFBPs secreted by bovine adrenocortical cells in primary culture, and investigated the
effect of corticotropin ( ACTH ) and recombinant human
IGF-I and IGF-II on the regulation of
IGFBP synthesis
Wilson et al., Eur J Endocrinol 1999
:
Taken together, these data suggest that, in the monkey,
IGFBP-3 is regulated by factors in addition to GH, and that
IGF-I can
affect its own bioavailability by increasing circulating concentrations of IGFBP-3
Schams et al., Domest Anim Endocrinol 1999
:
Studies indicate that
IGFBP expression and production in the developing follicle is dependent on both cell type and follicle size and is
regulated by
IGF-1 and gonadotropins
Pattison et al., Mol Cell Endocrinol 1999
(Breast Neoplasms) :
By contrast,
IGFBP-3 phosphorylation in T47D ( BP-3 ) cells was not
affected by retinoic acid or
IGF-I , but appeared slightly increased by estradiol
Hodgson et al., Regul Pept 2000
:
On the basis of such an experiment, performed at equilibrium,
IGFBP should
reduce the mitogenic activity of
IGF-1
Dahlfors et al., Endocrinology 2000
:
IGF-I , insulin, or angiotensin II did not
affect IGF-I or
IGFBP mRNA expression
Hayford et al., Growth Horm IGF Res 1998
:
IGF-I increased IGFBP-3 and
IGFBP-6 while decreasing IGFBP-4 ... These findings suggest that cAMP, dexamethasone and
IGF-I regulate
IGFBP production in human aorta smooth muscle cells via a complex interplay of changes in transcription, protease activation and dissociation of cell surface bound IGFBPs
Fottner et al., J Endocrinol 2001
:
In the present study, we identified and characterized IGFBP synthesis in normal adult human adrenocortical cells in primary culture, and investigated the
effect of ACTH and recombinant human
IGF-I and -II on the regulation of
IGFBP expression and secretion
Zeeh et al., Eur J Gastroenterol Hepatol 2001
(Colitis) :
Therefore, we investigated the expression of IGFBPs, collagen and collagenase activity in rat colitis and the
effects of
IGF-1 on
IGFBP and collagen expression in rat colonic smooth muscle cells
Laursen et al., FEBS Lett 2001
:
In the
presence of
IGF ,
IGFBP-4 and -5 are cleaved with similar rates by PAPP-A
Sprenger et al., J Endocrinol 2001
(Cell Transformation, Viral) :
Thus,
IGFBP-3 acts in an
IGF dependent manner to inhibit cell growth of benign prostate epithelial cells
Bostedt et al., Exp Cell Res 2001
(Bone Neoplasms...) :
We compared the growth rates,
IGFBP production, IGF I binding characteristics, IGF 1R protein and mRNA levels, and the acute
IGF I response ( stimulation of glycogen synthesis ) after pretreatment of the cells in serum-free medium with or without added IGF I or medium supplemented with 5 % fetal calf serum ( FCS )
Hsu et al., J Biol Chem 1992
:
The fasting induced increase in
IGFBP-30K is
inhibited by
IGF-I and by des-IGF-I and, to a lesser extent, by insulin ... Unlike cell associated IGFBP-30K, secretion of
IGFBP was
stimulated ( 6.8 +/- 0.5-fold, n = 2 ) by
IGF-I , whereas IGFBP secretion was inhibited 54 % by insulin ... These results demonstrate coordinate
regulation of
IGFBP by serum starvation and
IGF-I , such that at low concentrations of IGF-I, cell surface binding protein increases whereas binding protein secretion decreases
Hassager et al., J Clin Endocrinol Metab 1992
:
In addition,
IGF-I markedly
increased levels of the 29/32/34 kDa
IGFBP triplet in U-2 cells, but had little or no effect in the other human and rat osteosarcoma cell lines ... In addition,
IGF-I markedly
increased levels of the 29/32/34 kDa
IGFBP triplet in U-2 cells, but had little or no effect in the other human and rat osteosarcoma cell lines
Grimes et al., Endocrinology 1992
:
IGF-I , IGF-II, and the IGF-I analogs, but not insulin, also
induced production of an unidentified 30-kDa
IGFBP not normally detectable in these cultures ... IGF-I,
IGF-II , and the IGF-I analogs, but not insulin, also
induced production of an unidentified 30-kDa
IGFBP not normally detectable in these cultures
Baxter et al., J Endocrinol 1992
:
The binding proteins IGFBP-I and IGFBP-3 did not cross-react, but both
IGF-I and IGF-II markedly
inhibited IGFBP-6 tracer binding to antiserum
Martin et al., Endocrinology 1992
:
In this study we report that exogenous and endogenous IGFBP-3 inhibit production of an
IGF inducible
IGFBP
Kühl et al., Glia 2003
:
When added exogenously,
IGFBP-6 reduced O2A cell survival in the absence of
IGF-1 and inhibited IGF-1 stimulated survival in a partially IGF-1 dependent and partially IGF-1 independent fashion
Sirotkin et al., J Reprod Dev 2003
:
These observations demonstrate the
involvement of
IGF-I and OT in the control of ovarian follicular size and follicular cell proliferation, progestagen, estrogen,
IGFBP-3 , inhibin A and B secretion and in cAMP/PKA- and MAPK/ERK1 dependent intracellular mechanisms
Headey et al., J Mol Endocrinol 2004
(Colonic Neoplasms) :
In conclusion, both the N- and C-domains of IGFBP-6 are involved in IGF binding, the C-domain is responsible for the IGF-II binding preference of IGFBP-6 and intact
IGFBP-6 is
necessary for high affinity
IGF binding
King et al., Invest Ophthalmol Vis Sci 2004
:
IGFBP production by these cells is further
increased by
IGF-I and -II, growth factors known to be present and active in proliferative vitreoretinal disorders, suggesting that Müller cells represent a potential source of vitreous IGFBPs in disorders involving this cell type
Yoshida et al., J Periodontal Res 2005
(Gingival Hyperplasia) :
On the other hand, exogenous
IGF-I induced 8-11 % ( p < 0.05 ) increases in the proliferation, but cyclosporin A induced 30-80 % ( p < 0.05-0.01 ) reductions in the mRNA expression levels for endogenous IGF-I, IGFR1, IGFBP2, IGFBP3, IGFBP5, and
IGFBP6
Kiepe et al., Endocrinology 2005
:
We therefore studied the
effect of
IGF-I on
IGFBP synthesis and the involved intracellular signaling pathways in two cell culture models of rat growth plate chondrocytes
Fleming et al., J Endocrinol 2005
:
In BME cells,
IGFBP-6 protein levels were readily detectable under basal conditions and were
increased by
IGF-I
Moon et al., Int J Cancer 2006
(Carcinoma, Non-Small-Cell Lung...) :
However, under certain circumstances,
IGFBP-3 can
enhance the activity of
IGF by protecting IGF from degradation
Thraikill et al., J Clin Invest 1990
:
Cultured human decidual cells release three IGF-BPs with 24,000, 30,000, and 34,000 Mr. Using ligand blot analysis and an RIA for the 30,000-Mr form ( IGF-BP-1 ), we examined the
effects of
IGF-I ( 10-1,000 ng/ml ), insulin ( 10-10,000 ng/ml ), and relaxin ( 10-250 ng/ml ) on decidual cell
IGF-BP release after 120 h of hormone exposure
Conover et al., J Clin Invest 1991
(Cell Transformation, Viral) :
The
IGF-I induced change in
IGFBP levels was not a type I IGF receptor mediated effect on IGFBP synthesis because ( a ) high concentrations of insulin did not mimic IGF-I 's effect ; ( b ) IGF-II and IGF-I analogues having reduced affinity for the IGF-I receptor were equipotent with IGF-I in increasing medium IGFBPs ; ( c ) [ QAYL ] IGF-I, and IGF-I analogue having normal receptor affinity and decreased affinity for IGFBPs, had no effect ; and ( d ) alpha IR-3, a monoclonal antibody specific for the type I IGF receptor, did not block IGF-I stimulated increases in IGFBPs ... The IGF-I induced change in IGFBP levels was not a type I
IGF receptor mediated
effect on
IGFBP synthesis because ( a ) high concentrations of insulin did not mimic IGF-I 's effect ; ( b ) IGF-II and IGF-I analogues having reduced affinity for the IGF-I receptor were equipotent with IGF-I in increasing medium IGFBPs ; ( c ) [ QAYL ] IGF-I, and IGF-I analogue having normal receptor affinity and decreased affinity for IGFBPs, had no effect ; and ( d ) alpha IR-3, a monoclonal antibody specific for the type I IGF receptor, did not block IGF-I stimulated increases in IGFBPs
Gourmelen et al., Acta Paediatr Scand Suppl 1991
(Dwarfism) :
Subcutaneous injection of IGF-I, 40 micrograms/kg, provoked an increase in serum IGF-I levels to close to the lower limits of the normal range and a small increase in IGFBP-3, suggesting that IGF-I has a direct effect on the synthesis of this
GH/IGF-I dependent
IGFBP
Chesik et al., Cytokine Growth Factor Rev 2007
(Central Nervous System Neoplasms...) :
In particular,
IGFBP-2 plays a dominant role in
IGF regulation in the CNS and is upregulated in several pathological conditions, including MS
Durai et al., Colorectal Dis 2007
(Colorectal Neoplasms) :
Its binding proteins (
IGFBP ) are
involved in local regulation of
IGF
Bower et al., PloS one 2010
:
IGF-I and IGF-II directly
stimulated IGFBP-6 expression, but not when amino acids were present
Martin et al., Endocrinology 1990
(Cell Transformation, Neoplastic) :
These results indicate that
IGF-I and IGF-II
induce an
IGFBP that is different from previously characterized human IGFBPs
Ekström et al., Hormone research in pædiatrics 2011
(Insulin Resistance...) :
After 8 months without treatment, we examined the short- and long-term
effects of
IGF-I/BP-3-Tx and, subsequently, IGF-I-Tx on 12-hour overnight levels of
IGF-I , GH, insulin, IGFBP-1, insulin sensitivity by hyperinsulinemic euglycemic clamp, body composition by dual-energy X-ray absorptiometry and linear growth
Ritvos et al., Endocrinology 1988
(Choriocarcinoma...) :
34 K
IGF-BP inhibited the binding of [ 125I ] iodo- ( Thr59 )
IGF-I to JEG-3 monolayers in a concentration dependent manner by forming with the tracer a soluble complex that could not bind to the cell surface as demonstrated by competitive binding and cross linking experiments
McCusker et al., J Cell Physiol 1988
:
IGF-I , although it interferes with the assay and thereby lowers the amount of detectable IGF-BP,
stimulated the secretion of
IGF-BP from all three cell types
Pekonen et al., J Clin Endocrinol Metab 1988
:
Purified 34K
IGF-BP as well as decidual cytosols
inhibited [ 125I
] IGF-I binding to placental receptors ... Purified 34K
IGF-BP as well as decidual cytosols
inhibited [ 125I ]
IGF-I binding to placental receptors
Carlsson-Skwirut et al., Biochim Biophys Acta 1989
:
This biological activity of recombinant truncated
IGF-1 was not
affected by the
IGF-BP at concentrations which abolished the biological activity of recombinant IGF-1
Pekonen et al., Fertil Steril 1989
(Obesity...) :
The 34K IGF binding protein ( 34K
IGF-BP ) has been shown to
inhibit the binding of
IGF-I to its receptor
Lee et al., Pediatr Res 1989
(Growth Disorders...) :
IGF-BP25 has been shown to
inhibit IGF mitogenic action in vitro
Chen et al., J Cell Physiol 1994
(Breast Neoplasms...) :
Therefore,
IGFBP-3 secreted by MCF-7 cells can
enhance IGF-I stimulation of DNA synthesis, increase IGF-I binding to these cells, and prevent IGF-I induced desensitization of its own receptor, suggesting that IGFBP-3 plays a significant role in IGF-I mediated breast carcinoma proliferation
Irwin et al., Regul Pept 1993
:
We have investigated the
regulation by insulin,
IGF-I , and IGF-II, of
IGFBP secretion in human endometrial stromal cells decidualized in vitro, and examined the interrelationship between the induced changes in IGFBP levels and the biological responses of stromal cells to IGFs
McCarthy et al., J Cell Physiol 1994
:
By Western ligand blot analysis, 24 h treatment with PGE2 elevated the 24 and 38-47 kDa IGFBPs and to a lesser extent the 30/32 kDa complex, hGH elevated the 38-47 kDa IGFBPs, and
IGF-I and IGF-II each
increased the 30/32 kDa
IGFBP complex
Iwashita et al., Horm Res 1994
:
Similarly,
IGFBP-1 inhibited
125I-IGF-I binding to granulosa cells
Boney et al., Endocrinology 1994
:
The presence of a larger isoform of IGFBP-2 in a differentiation dependent manner and a potentially novel
IGFBP in
response to
IGF-I suggests that these IGFBPs may be important in modulating IGF-I action in adipogenesis
Conover et al., Endocrinology 1995
:
These data demonstrate that IGF peptide and glucocorticoid individually modulate IGFBP expression and indicate that glucocorticoid has distinct effects on
IGF regulation of
IGFBP depending upon the particular IGFBP and the underlying mechanism of IGF regulation
Duclos et al., Growth Regul 1994
(Liver Neoplasms, Experimental) :
This suggested that
IGF binding to LMH was
due mainly to membrane bound
IGFBP rather than to type 1 IGF receptors
McFarland et al., Gen Comp Endocrinol 1993
:
Equimolar levels of
IGF-I or insulin
stimulated IGFBP release, however, at levels lower than that induced by IGF-II
Benedict et al., J Gerontol 1994
:
In control animals, a striking
increase ( 143 % ) in the predominant 39-45 kDa serum
IGFBP ( BP-3 ), with little change in serum
IGF-I , accompanied the marked deceleration of growth which occurred between 2 and 8 months ; the levels of IGF-I and its BPs declined by 15 % and 34 %, respectively, later in life
Lee et al., J Clin Endocrinol Metab 1996
(Nephrotic Syndrome) :
We speculate that low serum
IGF-I and IGFBP-3 levels would be partially
due to the increased urinary losses of serum
IGF-IGFBP complexes, especially that of 150 kDa, and these changes may contribute to growth failure in persistent nephrotic syndrome
Grellier et al., J Endocrinol 1996
:
Since
IGF-I may
regulate IGFBP production, the effect of IGF-I on IGFBPs expressed by TC-1 cells was determined
Kummer et al., Endocrinology 1996
:
The stimulatory
effect of bFGF and
IGF-I on
IGFBP production was apparent after a 2- to 3-day exposure of the mesencephalic cultures to the peptides
Hembree et al., J Anim Sci 1996
:
Insulin-like growth factor binding proteins (
IGFBP ) may act locally as autocrine or paracrine
regulators of
insulin-like growth factor activity in specific tissues such as muscle
Arai et al., Endocrinology 1996
:
In summary,
IGFBP-2 binding to glycosaminoglycans is
dependent upon binding of
IGF-I and IGF-II to IGFBP-2
Chen et al., J Anim Sci 1996
:
We examined the time course of insulin-like growth factor binding protein (
IGFBP ) secretion and hormonal
regulation of IGFBP and
IGF-I secretion in porcine stromal vascular ( S-V ) cultures
Glander et al., Hum Reprod 1996
:
IGF-I is mainly controlled by concentrations of human growth hormone ( HGH ), influences cell proliferation and differentiation and its action is
mediated by insulin-like growth factor binding proteins (
IGFBP ), placental protein 14 (PP14) and prostate-specific antigen (PSA)
Monaco et al., J Endocrinol 1997
(Body Weight) :
The decrease in IGFBP-3 and increase in lower molecular weight
IGFBP may have
contributed to the reduction in serum
IGF-I by increasing IGF-I clearance from the circulation
Morales et al., Arch Biochem Biophys 1997
:
By contrast,
IGF-1 ( 10 ng/ml )
increased IGF-BP by < 2-fold ( n = 4 ), and retinoic acid, at 1 x 10 ( -8 ) M was not effective ( n = 3 )
Oguchi et al., Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi 1997
:
The
effects of
IGF-I and EGF on
IGFBP secretion diminished with increasing cell differentiation
Bach et al., J Endocrinol 1997
:
IGFBP-6 was not released from a cell associated reservoir or protected from proteolysis by IGFs, excluding these post-translational mechanisms as explanations for the
IGF effects on
IGFBP-6 levels
Giannini et al., Metabolism 1997
:
In fact, ( 1 ) IGFBP mRNA levels were not modified after stimulation with 100 nmol/L IGF-I, ( 2 ) 100 nmol/L
IGF plus an equimolar concentration of alpha IR3 did not
affect IGFBP production, ( 3 ) Des ( 1-3 ) IGF-I had no effect on IGFBP modulation, whereas at 10 nmol/L it enhanced BREC thymidine cell incorporation, and ( 4 ) 100 nmol/L insulin, which at this concentration can cross-react with the IGF-I receptor, did not modify the IGFBP pattern
McCusker et al., J Cell Physiol 1998
:
IGFBP secretion by L6 cells is
stimulated by both
insulin/IGF-I and cAMP dependent pathways, whereas IGFBP-5 secretion by BC3H-1 cells is stimulated only by the insulin/IGF pathway
Sunic et al., Endocrinology 1998
:
The aim of this study was to investigate the
effects of
IGF-I and IL-1 on
IGFBP production by ovine articular chondrocytes ( OAC ) and the roles of these IGFBPs in the regulation of proteoglycan synthesis
Cabrol et al., Arch Pediatr 1998
(Growth Disorders...) :
Elevated
IGFBP levels may
contribute to a reduced
IGF activity, especially in dialysed patients