インスリン様増殖因子結合タンパク質3、インスリン様成長因子結合タンパク質3

関: IGFBP-3

WordNet

want to have; "Id like a beer now!"
a kind of person; "Well not see his like again"; "I cant tolerate people of his ilk" (同)ilk
a similar kind; "dogs, foxes, and the like", "we dont want the likes of you around here" (同)the like, the likes of
equal in amount or value; "like amounts"; "equivalent amounts"; "the same amount"; "gave one six blows and the other a like number"; "the same number" (同)same
resembling or similar; having the same or some of the same characteristics; often used in combination; "suits of like design"; "a limited circle of like minds"; "members of the cat family have like dispositions"; "as like as two peas in a pod"; "doglike devotion"; "a dreamlike quality" (同)similar
be fond of; "I like my nephews"
feel about or towards; consider, evaluate, or regard; "How did you like the Presidents speech last night?"
find enjoyable or agreeable; "I like jogging"; "She likes to read Russian novels"
cultivate by growing, often involving improvements by means of agricultural techniques; "The Bordeaux region produces great red wines"; "They produce good ham in Parma"; "We grow wheat here"; "We raise hogs here" (同)raise, farm, produce
come to have or undergo a change of (physical features and attributes); "He grew a beard"; "The patient developed abdominal pains"; "I got funny spots all over my body"; "Well-developed breasts" (同)develop, produce, get, acquire
become attached by or as if by the process of growth; "The tree trunks had grown together"
become larger, greater, or bigger; expand or gain; "The problem grew too large for me"; "Her business grew fast"
cause to grow or develop; "He grows vegetables in his backyard"
increase in size by natural process; "Corn doesnt grow here"; "In these forests, mushrooms grow under the trees"; "her hair doesnt grow much anymore"
(biology) the process of an individual organism growing organically; a purely biological unfolding of events involved in an organism changing gradually from a simple to a more complex level; "he proposed an indicator of osseous development in children" (同)growing, maturation, development, ontogeny, ontogenesis
(pathology) an abnormal proliferation of tissue (as in a tumor)
a progression from simpler to more complex forms; "the growth of culture"
something grown or growing; "a growth of hair"
vegetation that has grown; "a growth of trees"; "the only growth was some salt grass"
be a contributing factor; "make things factor into a companys profitability"
any of the numbers (or symbols) that form a product when multiplied together
an independent variable in statistics
anything that contributes causally to a result; "a number of factors determined the outcome"
consider as relevant when making a decision; "You must factor in the recent developments" (同)factor in, factor out
resolve into factors; "a quantum computer can factor the number 15" (同)factor in, factor out
executed with proper legal authority; "a binding contract"
the protective covering on the front, back, and spine of a book; "the book had a leather binding" (同)book binding, cover, back
strip sewn over or along an edge for reinforcement or decoration
the capacity to attract and hold something

PrepTutorEJDIC

…‘を'『好む』,‘が'好きである / 《しばしば否定文で,またwould,《英》shouldと共に用いて》…‘を'望む,…したい / 『好む』;望む / 《複数形で》好み,好きな事
(外観・性質などが)…『に似た』,のような / (やり方,程度などが)…『と同じように』 / …『らしい』,にふさわいし / 《おもに話》たとえば…のような / 《名詞の前にのみ用いて》(性質・外観などが)同じの,(数量が)等しい / 《補語にのみ用いて》似ている,そっくりで / たぶん,おそらく(probably) / (…に)似た人(物),(…と)同等の人(物),匹敵する人(物)《+『of』+『名』》 / …のように / あたかも…のように
『成長する』,育つ,〈植物が〉生える,茂る / (類・量・程などにおいて)『増大する』,大きくなる / 『しだいになる』 / …‘を'成長させる,大きくする,育てる / …から生じる(起こる)
〈U〉(…の)『成長』,発育;『発達』,発展《+『of』+『名』》 / 〈U〉(数・量,重要性・力などの)『増加』,増大,拡張《+『of』+『名』》 / 〈U〉《修飾語[句]を伴って》栽培,生産,…産 / 〈C〉成育した物,(草,木,髪,ひげなどの)生えたもの / 〈C〉腫瘍(しゅよう)
(…の)『要因』,(…を生み出す)要素《+『in』+『名』(do『ing』)》 / 囲数,約数 / 代理人,《おもに英》仲買人 / =factorize
義務的な,拘束力ある / 〈U〉しばること;〈C〉しばる物 / 〈C〉製本,装丁 / 〈U〉縁(‘ふち')取り材料

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/11/03 11:39:21」(JST)

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Insulin-like growth factor-binding protein 3, also known as IGFBP-3, is a protein that in humans is encoded by the IGFBP3 gene. IGFBP-3 is one of six IGF binding proteins (IGFBP-1 to IGFBP-6) that have highly conserved structures and bind the insulin-like growth factors IGF-1 and IGF-2 with high affinity. IGFBP-7, sometimes inappropriately included in this family, shares neither the conserved structural features nor the high IGF affinity.

Function

IGFBP-3 was first isolated, characterized, and quantitated in human plasma, in 1986.^[1]^[2] It has well-documented functions in the circulation, in the extracellular environment, and inside cells. It is the main IGF transport protein in the bloodstream, where it carries the growth factors predominantly in stable complexes that contain the binding protein, either IGF-1 or IGF-2, and a third protein called the acid-labile subunit or ALS.

For IGFs to reach the tissues from the bloodstream, the circulating complexes are believed to partly dissociate, possibly enhanced by limited proteolysis of IGFBP-3. The IGF-1/IGFBP-3 ratio has sometimes been used as an index of IGF bioavailability in the human circulation, but this ignores IGF-1 binding to other IGFBPs (so the ratio is affected by the concentrations of all six IGFBPs), and the fact that IGF-2, which is three times more abundant than IGF-1 in the bloodstream of adults, occupies the majority of binding sites on circulating IGFBP-3.

Within tissues, IGFBP-3 can bind IGF-1 and IGF-2 released by many cell types, and block their access to the IGF-1 receptor (IGF1R), which is activated by both IGFs. IGFBP-3 also interacts with cell-surface proteins, affecting cell signaling from outside the cell or after internalization, and also enters the cell nucleus where it binds to nuclear hormone receptors and other ligands. High levels of IGFBP-3 within tumors are associated with increased cancer severity (or worse outcome) for some cancers, but decreased severity or better outcome for others. No cases of IGFBP3 gene deletion in humans have been reported, but mice lacking the gene show near-normal growth.

Gene and protein structure

The IGFBP3 gene (or IBP3), on human chromosome 7, is organized into four protein-coding exons with a 5th exon in the 3’ untranslated region.^[3] It is located adjacent to the IGFBP1 gene in tail-to-tail orientation, separated by 20 kb.^[4] The encoded protein includes a 27-residue signal peptide followed by the 264-residue mature protein. IGFBP-3 shares with the other five high-affinity IGFBPs and a 3-domain structure:^[5]

A conserved N-terminal domain containing a cysteine rich region (12 cysteine residues) with multiple intra-domain disulfide bonds, a IGFBP motif (GCGCCXXC), the primary site of IGF binding.
A highly variable central or linker domain (only 15% conservation between IGFBPs).
A conserved C-terminal domain containing secondary IGF binding residues, a cysteine rich region (6 cysteine residues), an 18 residue basic motif that binds heparin, the acid labile subunit (ALS), and a nuclear localization sequence.

The linker domain is the site of most post-translational modification, which include glycosylation, phosphorylation, and limited proteolysis. By electrophoretic analysis IGFBP-3 appears as a doublet, owing to the occupancy of either two or three of its N-glycosylation sites by carbohydrate. Hypoglycosylated IGFBP-3 may be seen after extended glucose starvation.

Many proteases are known to cleave IGFBP-3 at single linker-domain sites, and in the circulation of pregnant women, IGFBP-3 is entirely proteolyzed, yet still capable of carrying normal amounts of IGF-1 and IGF-2. Binding capacity appears to be retained after proteolysis because of a cooperative interaction between the two proteolyzed fragments, that together maintain an active IGF-binding site.^[6]

Sites and regulation of production

IGFBP-3 mRNA is expressed in all tissue examined, with kidney, stomach, placenta, uterus and liver showing highest expression in rat tissues.^[7] Rat liver IGFBP-3 mRNA is found in nonparenchymal cells including sinusoidal endothelium, but not in hepatocytes.^[8] In contrast, human hepatocytes do express IGFBP-3.^[9]

IGFBP-3 levels in human serum are, like IGF-1, dependent on growth hormone (GH); for example, serum IGFBP-3 is increased in acromegaly and low in GH-deficient children. However, IGFBP-3 gene expression in human liver is GH-independent.^[2]^[10] Because it is stabilized in human serum by forming complexes with IGF-1 and ALS, which are both GH-dependent, serum IGFBP-3 also appears regulated by GH. Its production by some non-hepatic tissues may also be directly GH-regulated. Immunoassays for serum IGFBP-3 are often used as part of the diagnosis of childhood GH-deficiency.

The most widely-studied IGFBP3 polymorphism, at nucleotide-202 in the promoter region, is significantly associated with circulating IGFBP-3 levels, although the mechanism is unclear.^[11] In some studies circulating IGFBP-3 also appears to be nutritionally regulated, although this may not be seen at the mRNA level. IGFBP-3 has been identified in human lymph, nipple aspirate, milk, amniotic fluid, follicular fluid, seminal plasma, urine, peritoneal dialysate, synovial fluid, tear fluid, and cerebrospinal fluid, in addition to serum.

Many factors increase IGFBP-3 production by cells, including transforming growth factor-β (TGFβ), tumor necrosis factor-α, vitamin D, retinoic acid, IGF-1, and stimuli such as chemotherapy that activate the tumor suppressor p53.^[12] Estrogen inhibits IGFBP-3 production, and its tissue levels are lower in estrogen receptor (ER)-positive breast cancers than in ER-negative cancers.

Interactions

The main IGFBP-3 ligands in the circulation are IGF-1 and IGF-2, and the acid-labile subunit (ALS).^[13] The serum proteins transferrin,^[14] fibronectin,^[15] and plasminogen^[16] are also known to bind IGFBP-3. In the cell and tissue environment many other interactions have been described (see Table). Two unrelated cell-surface proteins have been designated as IGFBP-3 receptors: low density lipoprotein receptor-related protein 1 (LRP1), also known as alpha-2-macroglobulin receptor or type V TGFβ receptor^[17] and the transmembrane protein TMEM219.^[18] Both are believed to mediate antiproliferative effects. Functional interactions with the EGF receptor and the type I/type II TGFβ receptor system have also been reported, and other cell-surface proteins such as proteoglycans also bind IGFBP-3. IGFBP-3 can enter cells by both clathrin-mediated and caveolin-mediated endocytosis.^[19] possibly involving the transferrin receptor.^[20]

IGFBP-3 enters the cell nucleus by a mechanism that is incompletely understood, but involves its binding to importin-β.^[21] Within the nucleus, it can modulate nuclear hormone receptor activity by direct binding to retinoid X receptor, retinoic acid receptor,^[22] vitamin D receptor,^[23] PPARγ,^[24] and nur77,^[25] IGFBP-3 also interacts with DNA-dependent protein kinase within the nucleus to promote the repair of DNA damage.^[26]

Cellular actions

IGFBP-3 exerts antiproliferative effects in many cell types by blocking the ability of IGF-1 and IGF-2 to activate the IGF1R (which stimulates cell proliferation). For example, in esophageal epithelial cells, responsiveness to IGF-1 stimulation is suppressed by secreted IGFBP-3 and restored when IGFBP-3 is downregulated by epidermal growth factor.^[27] IGFBP-3 can also inhibit cell function by mechanisms that are independent of effects on IGF1R signaling, even in cells that entirely lack IGF1R.^[28] IGF (or IGF1R) independent effects are commonly studied using mutant forms of IGFBP-3 with decreased IGF binding affinity. Thus, IGFBP-3-induced apoptosis in differentiating chondrocyte precursor cells is seen equally with a non-IGF binding IGFBP-3 mutant, demonstrating that the mechanism does not involve IGF binding.^[29] IGF1R-independent growth inhibition by IGFBP-3 may involve the induction of pro-apoptotic proteins such as Bax and Bad^[30] and may be mediated by ceramides (pro-apoptotic lipids),^[31] or potentiate ceramide action^[32] IGFBP-3 interaction with nuclear hormone receptors may also lead to inhibition of cell proliferation.

Contrasting with the typical growth-inhibitory effects of IGFBP-3, stimulation of cell proliferation by IGFBP-3 has also been observed. This can occur either by enhancing IGF-stimulated proliferation^[33] or in the absence of IGF-1. In endothelial cells and mammary epithelial cells, the stimulatory effect of IGFBP-3 has been shown to involve activation of the enzyme sphingosine kinase, and generation of the bioactive lipid, sphingosine-1-phosphate, which promotes growth by transactivating the EGFR receptor.^[31]^[34]

Role in cancer

Based on cell growth experiments, animal cancer models, and epidemiological studies, it appears that IGFBP-3 functions as a low-penetrance tumor suppressor gene.^[5]

Dysregulation of IGFBP-3 has been implicated in many cancers.^[35] IGFBP-3 is sometimes referred to as a tumor suppressor, and downregulation of its tissue expression by promoter hypermethylation in some cancers, such as hepatoma.^[36] and non-small cell lung cancer^[37] may be associated with poor patient outcome. However, consistent with the dual inhibitory and stimulatory roles of IGFBP-3 seen in cell culture, there are other cancer types, such as breast cancer,^[38]^[39] pancreatic cancer,^[40] and clear cell renal cell cancer^[41] in which high tissue IGFBP-3 expression has been linked to poor prognostic features or patient outcome. The mechanisms regulating these contrasting effects of IGFBP-3 in vivo are not well understood.

Since IGFBP-3 is abundant in the bloodstream of healthy adults (typically 2–4 mg/L), and is largely stabilized by its complex formation with IGFs and ALS, it is unlikely that tumor-derived IGFBP-3 has a large influence on circulating levels. There have been many studies linking circulating IGFBP-3 levels to the presence, or risk, of various cancers, or to patient outcomes.^[35] but unequivocal conclusions have often been lacking. For example, high plasma IGFBP-3 levels were associated with a reduced prospective risk of colorectal cancer in women.^[42] but in a study including men and women, colon cancer risk was positively associated with plasma IGFBP-3, while there was no significant association for rectal cancer.^[43] A large systematic review concluded that circulating IGFBP-3 levels showed a modest association with increased risk for a number of cancers, but the results vary among sites.^[44]

IGFBP-3 protein levels decrease during the progression of prostate cancer from benign to metastatic disease^[45] although production of the protein does not cease completely. IGFBP-3 is still made (at a lower level) by prostate cancer cells and secreted into the surrounding environment. However, instead of the full length, functional protein, IGFBP-3 is found to be cleaved.^[46] This decreases the affinity of IGF binding to IGFBP-3, making the growth factors more likely to bind the IGF1R and promote cell survival.

Table: IGFBP-3 binding partners

IGFBP3 has been shown to interact with:

ADAM12^[47]^[48]
ADAM28^[49]
COL1A1^[50]
FN1^[15]^[51]
IGFALS^[13]
IGF1,^[1]^[52]^[53]
IGF2^[1]^[52]
HSPA5^[54]
PLG^[16]
RXRA^[22]
TF^[14]^[55]
KPNB1^[21]
PRKDC^[26]
EGFR^[26]
LTBP1^[56]

References

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^ Palmqvist R, Hallmans G, Rinaldi S, Biessy C, Stenling R, Riboli E, Kaaks R (2002). "Plasma insulin-like growth factor 1, insulin-like growth factor binding protein 3, and risk of colorectal cancer: a prospective study in northern Sweden". Gut 50: 642–6. doi:10.1136/gut.50.5.642. PMID 11950809.
^ Renehan AG, Zwahlen M, Minder C, O'Dwyer ST, Shalet SM, Egger M (2004). "Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis". Lancet 363: 1346–53. doi:10.1016/s0140-6736(04)16044-3. PMID 15110491.
^ Miyake H, Pollak M, Gleave ME (June 2000). "Castration-induced up-regulation of insulin-like growth factor binding protein-5 potentiates insulin-like growth factor-I activity and accelerates progression to androgen independence in prostate cancer models". Cancer Res. 60 (11): 3058–64. PMID 10850457. For IGFBP-3 it refers to Figueroa JA, De Raad S, Tadlock L, Speights VO, Rinehart JJ (1998). "Differential expression of insulin-like growth factor binding proteins in high versus low Gleason score prostate cancer". J. Urol. 159 (4): 1379–83. doi:10.1016/S0022-5347(01)63620-6. PMID 9507888.
^ Birnbaum RS, Ware JL, Plymate SR (June 1994). "Insulin-like growth factor-binding protein-3 expression and secretion by cultures of human prostate epithelial cells and stromal fibroblasts". J. Endocrinol. 141 (3): 535–40. doi:10.1677/joe.0.1410535. PMID 7520932.
^ Shi Z, Xu W, Loechel F, Wewer UM, Murphy LJ (2000). "ADAM 12, a disintegrin metalloprotease, interacts with insulin-like growth factor-binding protein-3". J. Biol. Chem. 275 (24): 18574–80. doi:10.1074/jbc.M002172200. PMID 10849447.
^ Loechel F, Fox JW, Murphy G, Albrechtsen R, Wewer UM (2000). "ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3". Biochem. Biophys. Res. Commun. 278 (3): 511–5. doi:10.1006/bbrc.2000.3835. PMID 11095942.
^ Mochizuki S, Shimoda M, Shiomi T, Fujii Y, Okada Y (2004). "ADAM28 is activated by MMP-7 (matrilysin-1) and cleaves insulin-like growth factor binding protein-3". Biochem. Biophys. Res. Commun. 315 (1): 79–84. doi:10.1016/j.bbrc.2004.01.022. PMID 15013428.
^ Liu B, Weinzimer SA, Gibson TB, Mascarenhas D, Cohen P (2003). "Type Ialpha collagen is an IGFBP-3 binding protein". Growth Horm. IGF Res. 13 (2–3): 89–97. doi:10.1016/S1096-6374(03)00007-8. PMID 12735930.
^ Martin JA, Miller BA, Scherb MB, Lembke LA, Buckwalter JA (2002). "Co-localization of insulin-like growth factor binding protein 3 and fibronectin in human articular cartilage". Osteoarthr. Cartil. 10 (7): 556–63. doi:10.1053/joca.2002.0791. PMID 12127836.
^ ^a ^b Buckway CK, Wilson EM, Ahlsén M, Bang P, Oh Y, Rosenfeld RG (2001). "Mutation of three critical amino acids of the N-terminal domain of IGF-binding protein-3 essential for high affinity IGF binding". J. Clin. Endocrinol. Metab. 86 (10): 4943–50. doi:10.1210/jcem.86.10.7936. PMID 11600567.
^ Cohen P, Graves HC, Peehl DM, Kamarei M, Giudice LC, Rosenfeld RG (1992). "Prostate-specific antigen (PSA) is an insulin-like growth factor binding protein-3 protease found in seminal plasma". J. Clin. Endocrinol. Metab. 75 (4): 1046–53. doi:10.1210/jcem.75.4.1383255. PMID 1383255.
^ Grkovic S, O'Reilly VC, Han S, Hong M, Baxter RC, Firth SM (2013). "IGFBP-3 binds GRP78, stimulates autophagy and promotes the survival of breast cancer cells exposed to adverse microenvironments". Oncogene 32 (1): 2412–20. doi:10.1038/onc.2012.264. PMID 22751133.
^ Storch S, Kübler B, Höning S, Ackmann M, Zapf J, Blum W, Braulke T (2001). "Transferrin binds insulin-like growth factors and affects binding properties of insulin-like growth factor binding protein-3". FEBS Lett. 509 (3): 395–8. doi:10.1016/S0014-5793(01)03204-5. PMID 11749962.
^ Gui Y, Murphy LJ (2003). "Interaction of insulin-like growth factor binding protein-3 with latent transforming growth factor-beta binding protein-1". Mol. Cell. Biochem. 250: 189–95. doi:10.1023/A:1024990409102. PMID 12962157.

UpToDate Contents

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1. インスリン様成長因子 Iの生理学 physiology of insulin like growth factor i
2. 小児における成長ホルモン欠乏症の診断 diagnosis of growth hormone deficiency in children
3. 先端巨大症の診断 diagnosis of acromegaly
4. 大腸癌：疫学、危険因子、および防御因子 colorectal cancer epidemiology risk factors and protective factors
5. 低身長の原因 causes of short stature

English Journal

Insulin-Like Growth Factor 1 and Insulin-Like Growth Factor-Binding Protein 3 in Relation to the Risk of Type 2 Diabetes Mellitus: Results From the EPIC-Potsdam Study.

Drogan D, Schulze MB, Boeing H, Pischon T.
American journal of epidemiology.Am J Epidemiol.2016 Mar 15;183(6):553-60. doi: 10.1093/aje/kwv188. Epub 2016 Feb 14.
Higher levels of insulin-like growth factor-binding protein 3 (IGFBP-3) might raise the risk of type 2 diabetes mellitus (T2DM) via binding of insulin-like growth factor 1 (IGF-1), an insulin-like hormone that is involved in glucose homeostasis. We investigated serum concentrations of IGF-1 and IGFB
PMID 26880678

CRM1 inhibition promotes cytotoxicity in Ewing sarcoma cells by repressing EWS-FLI1-dependent IGF-1 signaling.

Sun H1, Lin DC2, Cao Q2, Guo X3, Marijon H2, Zhao Z4, Gery S2, Xu L5, Yang H6, Pang B7, Lee VK8, Lim HJ7, Doan N9, Said JW10, Chu P11, Mayakonda A5, Thomas T2, Forscher C3, Baloglu E12, Shacham S13, Rajalingam R14, Koeffler HP3.
Cancer research.Cancer Res.2016 Mar 8. pii: canres.1572.2015. [Epub ahead of print]
Ewing sarcoma (EWS) is an aggressive bone malignancy that mainly affects children and young adults. The mechanisms by which EWS (EWSR1) fusion genes drive the disease are not fully understood. CRM1 (XPO1) traffics proteins from the nucleus, including tumor suppressors and growth factors, and is over
PMID 26956669

Evaluating serum insulin-like growth factor 1 and insulin-like growth factor binding protein 3 as markers in prostate cancer diagnosis.

Rainato G1, Fabricio AS2, Zancan M1, Peloso L2, Dittadi R3, Barichello M4, Fandella A5, Scattoni V6, Gion M2.
The International journal of biological markers.Int J Biol Markers.2016 Mar 7:0. doi: 10.5301/jbm.5000200. [Epub ahead of print]
BACKGROUND: Prostate-specific antigen (PSA) lacks specificity and sensitivity in discriminating prostate cancer (PCa) from benign prostatic hyperplasia (BPH) when the total PSA (tPSA) level is between 4 and 10 ng/mL. It remains to be investigated if additional tumor-associated molecules may improve
PMID 26954072

Japanese Journal

Possible involvement of insulin-like growth factor 2 mRNA-binding protein 3 in zebrafish oocyte maturation as a novel cyclin B1 mRNA-binding protein that represses the translation in immature oocytes

Takahashi Kazuki,Kotani Tomoya,Katsu Yoshinao,Yamashita Masakane
Biochemical and Biophysical Research Communications 448(1), 22-27, 2014-05-23
… Besides cytoplasmic polyadenylation element-binding protein (CPEB) and cis-acting elements in the 3' untranslated region (UTR), Pumilio1 and a cis-acting element in the coding region of cyclin B1 mRNA are important for the subcellular localization and timing of translational activation of the mRNA. …
NAID 120005457022

CC Chemokine Ligand 18 and IGF-Binding Protein 6 as Potential Serum Biomarkers for Prostate Cancer

Xu Yong,Zhang Lei,Sun Sheng-kun,Zhang Xu
The Tohoku Journal of Experimental Medicine 233(1), 25-31, 2014
… indicated that serum levels of macrophage colony-stimulating factor (M-CSF) and CC chemokine ligand 18 (CCL-18) were remarkably higher in PCa patients than those in BPH patients, while serum levels of insulin-like growth factor-binding protein 6 (IGFBP-6) and Fas receptor (Fas), also called tumor necrosis factor receptor superfamily member 6 (TNFRSF6), were significantly …
NAID 130004822410

Inhibitory effect of insulin-like growth factor-binding protein-7 (IGFBP7) on in vitro angiogenesis of vascular endothelial cells in the rat corpus luteum

TAMURA Kazuhiro,YOSHIE Mikihiro,HASHIMOTO Keisuke [他],TACHIKAWA Eiichi
Journal of Reproduction and Development 60(6), 447-453, 2014
… To explore the physiological significance of insulin-like growth factor-binding protein-7 (IGFBP7) in the developing CL, the effects of IGFBP7 on vascular endothelial growth factor (VEGFA)- and luteinizing hormone (LH)-induced in vitro tube formation were tested using isolated luteal microvascular endothelial cells (LECs). …
NAID 130004774173

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★リンクテーブル★

リンク元	「IGFBP-3」「インスリン様増殖因子結合タンパク質3」「インスリン様成長因子結合タンパク質3」
関連記事	「binding」「like」「grow」「fact」「factor」

「IGFBP-3」

Insulin-like growth factor binding protein 3
Identifiers
Symbols	IGFBP3 ; BP-53; IBP3
External IDs	OMIM: 146732 MGI: 96438 HomoloGene: 500 ChEMBL: 3997 GeneCards: IGFBP3 Gene
Gene ontology
Molecular function	• fibronectin binding; • protein binding; • insulin-like growth factor binding; • protein tyrosine phosphatase activator activity; • insulin-like growth factor I binding; • insulin-like growth factor II binding; • metal ion binding;
Cellular component	• extracellular region; • extracellular space; • nucleus; • insulin-like growth factor binding protein complex; • insulin-like growth factor ternary complex; • extracellular exosome;
Biological process	• regulation of cell growth; • osteoblast differentiation; • negative regulation of protein phosphorylation; • protein phosphorylation; • apoptotic process; • negative regulation of cell proliferation; • negative regulation of signal transduction; • regulation of glucose metabolic process; • negative regulation of smooth muscle cell migration; • positive regulation of apoptotic process; • positive regulation of catalytic activity; • positive regulation of MAPK cascade; • regulation of insulin-like growth factor receptor signaling pathway; • positive regulation of insulin-like growth factor receptor signaling pathway; • cellular protein metabolic process; • type B pancreatic cell proliferation; • positive regulation of myoblast differentiation; • negative regulation of smooth muscle cell proliferation;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;