scholarly journals GRP94 Is Essential for Mesoderm Induction and Muscle Development Because It Regulates Insulin-like Growth Factor Secretion

2007 ◽  
Vol 18 (10) ◽  
pp. 3764-3775 ◽  
Author(s):  
Sherry Wanderling ◽  
Birgitte B. Simen ◽  
Olga Ostrovsky ◽  
Noreen T. Ahmed ◽  
Shawn M. Vogen ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Muscle Development ◽  
Es Cells ◽  
Primitive Streak ◽  
Mesoderm Induction ◽  
Insulin Like Growth Factor ◽  
Mouse Development ◽  
Factor Ii ◽  
Insulin Like Growth Factors

Because only few of its client proteins are known, the physiological roles of the endoplasmic reticulum chaperone glucose-regulated protein 94 (GRP94) are poorly understood. Using targeted disruption of the murine GRP94 gene, we show that it has essential functions in embryonic development. grp94−/− embryos die on day 7 of gestation, fail to develop mesoderm, primitive streak, or proamniotic cavity. grp94−/− ES cells grow in culture and are capable of differentiation into cells representing all three germ layers. However, these cells do not differentiate into cardiac, smooth, or skeletal muscle. Differentiation cultures of mutant ES cells are deficient in secretion of insulin-like growth factor II and their defect can be complemented with exogenous insulin-like growth factors I or II. The data identify insulin-like growth factor II as one developmentally important protein whose production depends on the activity of GRP94. Keywords: chaperone/HSP90/Insulin-like growth factors/mouse development.

Radioimmunoassay of insulin-like growth factors in cyst fluid of central nervous system tumors

1991 ◽  
Vol 74 (6) ◽  
pp. 972-978 ◽  
Author(s):  
Roberta P. Glick ◽  
Terry G. Unterman ◽  
Robert Hollis
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Cyst Fluid ◽  
Cns Tumors ◽  
Insulin Like Growth Factor ◽  
Content Type ◽  
Factor Ii ◽  
Spinal Schwannoma ◽  
Insulin Like Growth Factors

✓ Tumor cells are characterized by abnormalities in growth and metabolism, including the autocrine secretion of certain growth factors. The authors have previously shown the presence of insulin-like growth factor receptors in tumors of the central nervous system (CNS) and in this study examine whether CNS tumors are capable of autocrine secretion of insulin-like growth factors in situ. To investigate the production of insulin-like growth factors I and II by CNS tumors, the authors have developed specific radioimmunoassays for these growth factors. In situ production of insulin-like growth factors was studied by immunoassay of CNS tumor cyst fluid aspirated at the time of surgery from 12 cystic tumors: seven primary brain tumors, four metastatic tumors, and one spinal schwannoma. For immunoassay, cyst fluid was treated overnight with acetic acid, then insulin-like growth factors were separated from binding proteins by a refined solid-phase technique, then dried and reconstituted in immunoassay buffer. Normal human serum and cerebrospinal fluid served as controls. Insulin-like growth factor I was detected in all 12 tumors studied. In contrast, insulin-like growth factor II was detected only in three low-grade astrocytomas, the spinal schwannoma (which had the highest insulin-like growth factor II level of all tumors studied), and three metastatic lung cancers. These results suggest that CNS tumors may be capable of autocrine production of insulin-like growth factors in situ. Furthermore, there appears to be a difference in the type of insulin-like growth factors produced by different types of CNS tumors. Preferential production of insulin-like growth factors may be an important marker of tumor differentiation and useful as a diagnostic tool.

Receptors for Insulin-Like Growth Factors and Growth Effects of Multiplication-Stimulating Activity (Rat Insulin-Like Growth Factor II) in Rat Embryo Fibroblasts*

Endocrinology ◽  
1983 ◽  
Vol 112 (3) ◽  
pp. 971-978 ◽  
Author(s):  
SALLIE O. ADAMS ◽  
S. PETER NISSLEY ◽  
MASATO KASUGA ◽  
THOMAS P. FOLEY ◽  
MATTHEW M. RECHLER
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Rat Embryo ◽  
Growth Effects ◽  
Factor Ii ◽  
Embryo Fibroblasts ◽  
Insulin Like Growth Factors

Influence of insulin-like growth factor-binding protein-2 on plasma clearance and transfer of insulin-like growth factors-I and -II from plasma into mammary-derived lymph and milk of goats

1996 ◽  
Vol 150 (1) ◽  
pp. 121-127 ◽  
Author(s):  
C G Prosser ◽  
J Schwander
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Plasma Clearance ◽  
Binding Protein ◽  
Plasma Concentrations ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Lactating Goats ◽  
Igf I ◽  
Insulin Like Growth Factors

Abstract Plasma clearance of insulin-like growth factors-I and -II (IGF-I and -II) and insulin-like growth factor-binding protein-2 (IGFBP-2) from lactating goats (n=4) was determined following a single intravenous injection of the corresponding 125I-labelled human protein. Transfer of these proteins out of the vascular space was monitored by their subsequent appearance in mammary-derived lymph and milk. Clearance of 125I-IGFBP-2 from circulation was 0·37 ± 0·06 ml/min/kg, which is markedly greater than that of 125I-IGF-I or -II (0·11 ± and 0·12 ± 0·01 ml/min/kg respectively). This was also reflected in longer elimination half-lives for IGF-I (353 ± 6 min) and -II (254 ± 8 min) compared with IGFBP-2 (110 ± 9 min). Three hours after injection of the 125I-labelled protein, the plasma:lymph ratio of trichloroacetic acid-precipitable radioactivity was 1·54 ±0·04, 3·3 ±0·6 and 4·1 ±0·4 for IGFBP-2, IGF-I and -II respectively. The form of 125I-IGFBP-2 in lymph was not different from that of plasma. Elevation of plasma concentrations of IGFBP-2 by its intravenous infusion significantly decreased plasma half-life of both IGF-I and -II (251 ± 8 and 198 ±7 min respectively). Although the amount and rate of transfer of IGF into mammary-derived lymph was decreased slightly by IGFBP-2, concentrations eventually obtained were not different from control. However, secretion of IGFs into milk was significantly reduced by IGFBP-2, particularly in the case of IGF-I. These results are consistent with the ability of all three compounds to cross the vascular endothelium intact and of IGFBP-2 to decrease the uptake of IGF by mammary epithelium and subsequent secretion into milk. IGFBP-2 may well have acted to target plasma IGF towards non-mammary tissues, thus explaining the more rapid plasma clearance of IGFs in the presence of elevated IGFBP-2. Journal of Endocrinology (1996) 150, 121–127

Pattern of the insulin-like growth factor II gene expression during early mouse embryogenesis

Development ◽  
1990 ◽  
Vol 110 (1) ◽  
pp. 151-159 ◽  
Author(s):  
J.E. Lee ◽  
J. Pintar ◽  
A. Efstratiadis
Keyword(s):  
Growth Factor ◽  
Immunohistochemical Analysis ◽  
Primitive Streak ◽  
Insulin Like Growth Factor ◽  
Surface Ectoderm ◽  
Factor Ii ◽  
Extraembryonic Mesoderm ◽  
Early Mouse ◽  
Lateral Mesoderm

The mouse insulin-like growth factor II (IGF-II) gene encodes a polypeptide that plays a role in embryonic growth. We have examined the temporal and spatial pattern of expression of this gene in sections of the mouse conceptus between embryonic days 4.0 and 8.5 by in situ hybridization. Abundant IGF-II transcripts were detected in all the trophectodermal derivatives, after implantation. Labeling was then observed in primitive endoderm, but was transient and disappeared after formation of the yolk sac. Expression was next detected in extraembryonic mesoderm at the early primitive streak stage. Labeling in the embryo proper appeared first at the late primitive streak/neural plate stage in lateral mesoderm and in anterior-proximal cells located between the visceral endoderm and the most cranial region of the embryonic ectoderm. The position of the latter cells suggests that their descendants are likely to participate in the formation of the heart and the epithelium of the ventral and lateral walls of the foregut, where intense labeling was observed at the neural fold stage. Hybridization was also detected in cranial mesenchyme, including neural crest cells. The intensity of hybridization signal increased progressively in paraxial (presomitic and somitic) mesoderm, while declining in the ectoplacental cone. The neuroectoderm and surface ectoderm did not exhibit hybridization at any stage. Immunohistochemical analysis indicated co-localization of IGF-II transcripts, translated pre-pro-IGF-II, and the cognate IGF-II/mannose-6-phosphate receptor. These correlations are consistent with the hypothesis that IGF-II has an autocrine function.

Insulin and insulin-like growth factor I (IGF I) in early mouse embryogenesis

Development ◽  
1990 ◽  
Vol 108 (3) ◽  
pp. 491-495
Author(s):  
R. Spaventi ◽  
M. Antica ◽  
K. Pavelic
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Indirect Evidence ◽  
Mouse Embryos ◽  
Insulin Like Growth Factor ◽  
Embryonic Cells ◽  
Mouse Development ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Growth factors have an important role in the regulation of cell growth, division and differentiation. They are also involved in the regulation of embryonic growth and differentiation. Insulin and insulin-like growth factor I (IGF I) play an important part in these events in the later stages of embryogenesis, when organogenesis is completed. In this study, we are presenting evidence that insulin and IGF I are also secreted by embryonic tissues during the prepancreatic stage of mouse development. We found measurable amounts of insulin and IGF I in 8- to 12-day-old mouse embryos. We also showed that embryonic cells derived from 8-, 9- and 10-day-old mouse embryos secrete insulin, IGF I and/or related molecules. Furthermore, the same growth factors, when added to the culture of 9-day-old mouse embryonic cells, stimulate their proliferation. These results lead to the conclusion that insulin can stimulate the growth of embryonic cells during the period when pancreas is not yet formed, which is indirect evidence for a paracrine (or autocrine) type of action.

scholarly journals Insulin-like growth factor II (IGF-II) mRNA expression during skeletal muscle development of double-muscled and normal bovine foetuses

1999 ◽  
Vol 39 (1) ◽  
pp. 113-124 ◽  
Author(s):  
Anne Listrat ◽  
Lucette Belair ◽  
Brigitte Picard ◽  
Nathalie Boulle ◽  
Yves Geay ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Mrna Expression ◽  
Muscle Development ◽  
Insulin Like Growth Factor ◽  
Skeletal Muscle Development ◽  
Factor Ii

Calcium Signalling System Triggered by INsulin-Like Growth Factor II

Physiology ◽  
1989 ◽  
Vol 4 (3) ◽  
pp. 94-97
Author(s):  
I Nishimoto ◽  
I Kojima
Keyword(s):  
Growth Factors ◽  
Dna Replication ◽  
Growth Factor ◽  
Calcium Influx ◽  
Calcium Signalling ◽  
Insulin Like Growth Factor ◽  
Permeable Channel ◽  
Signalling System ◽  
Factor Ii ◽  
Epidermal Growth

In BALB/c 3T3 fibroblast, the insulin-like growth factor (IGF-II) stimulates DNA replication when added to cells pretreated sequentially with platelet-derived and epidermal growth factors. In these cells, IGF-II increases calcium influx by opening a voltage-independent calcium-permeable channel, and calcium influx is an intracellular message of the IGF-II action.

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