Biomedical subjects

C T Roberts

Publications and source records attributed to C T Roberts.

At least 55 records · Page 3Linked to original sources

PubMed1996

Interaction between the insulin receptor and its downstream effectors. Use of individually expressed receptor domains for structure/function analysis.

A structural analysis has been carried out to determine which part of the intracellular domain of the insulin receptor (IR) beta subunit is involved in direct interaction with the receptor substrates IRS-1 and Shc. Toward this end, the juxtamembrane (JM) domain (amino acids 943-984) and the carboxyl-terminal (CT) region (amino acids 1245-1 331) of IR were expressed in bacteria as (His)6-fusion peptides, and their interaction with IRS-1 and Shc was studied. We could demonstrate that the CT region of IR was sufficient to bind Shc, although significant, but much lower binding of Shc to the JM region could be detected as well. Furthermore, in vitro Tyr phosphorylation of the CT region potentiated its interactions with Shc 2-fold. In contrast, the JM region, but not the CT domain of the IR, was sufficient to mediate interactions between the IR and IRS-1. These interactions did not involve the pleckstrin homology (PH) region of IRS-1, since an IRS-1 mutant, in which four "blocks" of the PH domain (Pro5-Pro65) were deleted, interacted with the JM region of IR with the same efficiency as native IRS-1. These results suggest that the IR interacts with its downstream effectors through distinct receptor regions, and that autophosphorylation of Tyr residues located at the CT domain of the IR can modulate these interactions.

Animals↗

PubMed1996

Growth hormone (GH) status regulates GH receptor and GH binding protein mRNA in a tissue- and transcript-specific manner but has no effect on insulin-like growth factor-I receptor mRNA in the rat.

The effect of growth hormone-deficiency (GHD) and treatment with recombinant bovine GH (bGH) or human IGF-I (hIGF-I) for 10 days on the expression of GH receptor (GHR), GH binding protein (GHBP) and of insulin-like growth factor-I receptor (IGF-IR) mRNA was examined using dw/dw and normal Lewis rats. Hepatic GHR and GHBP mRNA expression was significantly lower in dw/dw rats in comparison to Lewis rats (P < 0.01) while specific 125I-bGH binding to hepatic microsomal membranes was significantly higher (P < 0.01), suggesting a reduction in hepatic GHR turnover with GHD. Treatment with bGH reduced hepatic specific 125I-bGH binding in dw/dw rats, but had no effect in Lewis rats. Treatment with hIGF-I increased hepatic specific 125I-bGH binding in Lewis rats. Hepatic GHR and GHBP mRNA expression was not changed by bGH or hIGF-I treatment, suggesting that differences in hepatic specific 125I-bGH binding may be due to posttranscriptional mechanisms. GHBP mRNA expression was higher in kidney, heart, and muscle of dw/dw rats in comparison to Lewis rats (P < 0.01), while GHR mRNA abundance was not changed. Treatment of dw/dw rats with hIGF-I or bGH resulted in a coordinate reduction of GHR and GHBP mRNAs in kidney (P < 0.01). IGF-IR mRNA was not detected in liver and despite reduced plasma IGF-I levels and IGF-I mRNA expression IGF-IR mRNA abundance was not changed in nonhepatic tissues by GHD. Our data suggest that changes in plasma IGF-I levels and local IGF-I mRNA do not influence IGF-IR mRNA expression, while GHR and GHBP mRNA expression in different rat tissues are regulated independently. The increased nonhepatic GHBP mRNA expression with GHD suggests that nonhepatic GHBP may have an important physiological function distinct from that of GHBP in liver or in plasma.

Animals↗

PubMed1996

Lack of association of trinucleotide repeat polymorphisms in very-low-density lipoprotein receptor gene with Alzheimer's disease.

Inheritance of the apolipoprotein E epsilon 4 allele is a risk factor for Alzheimer's disease (AD). A recent report studying Japanese patients suggested that a polymorphism of a trinucleotide repeat in the 5' untranslated region of an apolipoprotein E receptor, the very-low-density lipoprotein receptor, is genetically associated with AD, with overrepresentation of the allele containing five copies of the repeat. We determined the allele frequencies of the very-low-density lipoprotein receptor in 3 white populations totaling 469 individuals. In contrast to the previous report, we found no differences in allele frequencies between case patients and control subjects. The discrepancy could be due to differences in Japanese and white populations. Nonetheless, these data weaken the likelihood that this polymorphism in the very-low-density lipoprotein receptor gene is strongly associated with AD.

Alleles↗

PubMed1996

Regulation of insulin-like growth factor I receptor gene expression by the Wilms' tumor suppressor WT1.

THe insulin-like growth factor I receptor (IGF-I-R) has been implicated in the etiology and/or progression of Wilms' tumor, or nephroblastoma, a pediatric neoplasm of the kidney that is often associated with deletion or mutation of the WT1 tumor suppressor gene. The levels of IGF-I-R mRNA in the tumors were sixfold higher than in normal adjacent kidney tissue and were inversely correlated to the levels of WT1 mRNA, suggesting that the expression of the IGF-I-R gene is under inhibitory control by WT1. Cotransfection of an IGF-I-R promoter-luciferase reporter construct together with a WT1 expression vector resulted in a dose-dependent suppression of promoter activity. Multiple WT1 binding sites were mapped in the 5'-flanking and 5'-untranslated regions of the IGF-I-R gene using gel retardation and DNaseI footprinting assays. Thus, suppression of the IGF-I-R promoter by WT1 involves multiple interactions of its zinc finger domain with sites located both upstream and downstream of the transcription initiation site. Finally, we showed that expression of the endogenous IGF-I-R gene is decreased in G401 cells stably transfected with a WT1 expression vector. Reduction in expression of the IGF-I-R gene is associated with a decrease in a number of IGF-I-mediated biological effects. Thus, deletion or mutation of the WT1 gene in Wilms' tumor and other malignancies can result in overexpression of the receptor, with enhanced autocrine/paracrine activation by locally produced or circulating IGFs.

Animals↗

PubMed1996

The marsupial shell membrane: an ultrastructural and immunogold localization study.

In the dasyurid marsupial, Sminthopsis crassicaudata, as the oocytes/embryos travel down the female reproductive tract two extracellular coats, the mucoid and shell membrane, come to surround them. Embryos recovered from the oviduct have a mucoid coat but no shell membrane which is only found surrounding uterine embryos. Initially, the shell membrane has a compact granular consistency but it later thins and becomes fibrous in texture with fibres oriented mainly in the plane of the membrane. Immunogold labelling with polyclonal antibodies raised against the extracellular coats was employed to determine the location and ultrastructural appearance of the secretory granules which contain mucoid and shell membrane precursors. Secretory granules in the luminal epithelium of the ampulla of the oviduct are of irregular electron density, while those in the isthmus are electron-dense and homogeneous. Both types give rise to the mucoid coat. Secretory granules in the epithelia of the utero-tubal junction and some endometrial glands are electron-lucent and contain some flocculent material which, after exocytosis, gives rise to the shell membrane.

Animals↗

PubMed1996

Digital imaging of cephalometric radiographs, Part 2: Image quality.

The aim of this study was to compare the diagnostic quality of conventional cephalometric radiographs with that of digital image counterparts. The random error associated with angular and linear measurements recorded on the digital images was greater than on the conventional radiographs. In addition, there was a systematic error producing statistically significant differences in the majority of angular and linear measurements between the digital images and the conventional radiographs. The errors that occurred with some measurements were of sufficient magnitude to be of clinical significance, particularly in a cephalometric situation where a high degree of accuracy is required. It is therefore suggested that, for digital imaging of cephalometric radiographs, a pixel matrix larger than 512 x 512 with more than 64 gray levels is required to maintain the diagnostic quality of the original radiograph.

Cephalometry↗

PubMed1996

Variation in ultrastructure of mucoid coat and shell membrane secretion of a dasyurid marsupial.

In the dasyurid marsupial Sminthopsis crassicaudata, the shell membrane of cleaving embryos has a compact granular structure but becomes fibrous around blastocysts. Polyclonal antibodies were raised against the extracellular coats, mucoid and shell membrane, of oocytes and early embryos. Immunogold cytochemistry resulted in labelling of secretory granules in the epithelia of both the ampulla and isthmus of the oviduct, although the secretory granules of these two regions differed in their ultrastructural appearance. Those in the ampulla were heterogeneous with areas of varying electron density, whereas those in the isthmus were electron dense and homogeneous. Shell membrane precursors were found in secretory granules in the epithelia of the uterotubal junction and endometrial glands and were electron lucent.

Animals↗

PubMed1996

Changes in structure of the trophectoderm of a marsupial in Mid-pregnancy up to the time of implantation.

Pre- and peri-implantation embryos of the dasyurid marsupial Sminthopsis crassicaudata were examined for morphological differentiation of the trophectoderm. The cells of unilaminar blastocysts were all squamous and stained intensely with toluidine blue. In bilaminar blastocysts and embryos at the early embryonic-disc stage, the trophectoderm was similar in appearance to, but stained more lightly than, the underlying endoderm. Trophoblast differentiation did not appear to occur until the mesoderm had begun to migrate between the trophoblast and endoderm beyond the embryonic disc. At this stage, trophoblasts had three distinct morphologies: (1) vacuolated, tall and columnar cells in the trilaminar region; (2) large cuboidal cells in the adjacent bilaminar region; and (3) squamous cells in the abembryonic pole of the bilaminar region. These variations in cell structure correlate with differences in subsequent functional activity in these three regions of the yolk sac placenta.

Animals↗

PubMed1996

Effect of hypoxia on lung, heart, and liver insulin-like growth factor-I gene and receptor expression in the newborn rat.

OBJECTIVES: We examined the effect of 7 days of hypoxia in the newborn rat on: a) body, heart, and lung growth; b) circulating insulin-like growth factor-I (IGF-I); c) lung, heart, and liver IGF-I gene expression; and d) lung IGF-I type 1 receptor gene expression and IGF-I receptor binding. We hypothesize that hypoxic exposure would modify body and organ growth and alter IGF-I gene and receptor expression in an organ specific manner. DESIGN: Randomized, controlled prospective study. SETTING: University research laboratory. SUBJECTS: Eleven newborn rat litters (n = 10 per litter) comprised the hypoxia-exposed group and 11 litters comprised the control group (room air). INTERVENTIONS: Hypoxia-group rats were placed in a chamber with an FIO2 of 0.12 on postnatal day 1. Control group rats breathed room air. Exposure to hypoxia continued for 7 days. MEASUREMENTS AND MAIN RESULTS: Hepatic, lung, and cardiac IGF-I mRNA levels and lung IGF-I type 1 receptor mRNA were analyzed, using the ribonuclease protection assay. Crude membrane extracts were used for competitive binding studies with IGF-I and insulin. Somatic growth in the hypoxic group was reduced by 22% (final weight: hypoxic, 14.8 +/- 1.2 g; control, 17.1 +/- 1.5 g; p < .001). The relative weight (organ weight/body weight [mg/g]) of the heart was increased by 39% (p < .001) in the hypoxic pups compared with the normoxic animals, while the relative weight of the lung was unchanged. With hypoxia, IFG-I mRNA concentrations were significantly increased both in the heart and lung (30% and 33%, respectively, p < .02); but, in contrast, IGF-I mRNA concentrations were not significantly different in the liver. The IGF-I receptor mRNA in the lung was increased by 200% (p < .02) in hypoxia compared with controls. There was no effect of hypoxia on specific or nonspecific binding of IGF-I or insulin in the lung tissue. However, specific binding was 33% greater in the IGF-I compared with the insulin experiments. CONCLUSIONS: a) Hypoxia increased IGF-I mRNA in the heart, and increased both IGF-I mRNA and IGF-I type 1 receptor mRNA in the lung. b) The effects of hypoxia on IFG-I are tissue-specific.

Animals↗

PubMed1996

Tumorigenic and mitogenic capacities are reduced in transfected fibroblasts expressing mutant insulin-like growth factor (IGF)-I receptors. The role of tyrosine residues 1250, 1251, and 1316 in the carboxy-terminus of the IGF-I receptor.

Regulation of ligand-mediated signal transduction through transmembrane tyrosine kinase growth factor receptors involves phosphorylation of tyrosine residues in the intracellular domain of the receptor. The insulin-like growth factor-I (IGF-I) receptor contains three tyrosine residues in the carboxy-terminal domain at positions 1250, 1251, and 1316. Of these, only the tyrosine at position 1316 is conserved in the homologous position of the insulin receptor. Mutational analysis was used to study the role of these tyrosines in specific outcomes of IGF-I-mediated signal transduction. Mutations in the human IGF-I receptor were either replacement of tyrosines 1250 and 1251 with phenylalanine and histidine (yyFH), respectively, or replacement of the conserved distal tyrosine (position 1316) with phenylalanine (yCF). The yyFH mutation results in an IGF-I receptor with the amino acids found in the homologous position of the human insulin receptor. Cells overexpressing mutated IGF-I receptors were compared with cells expressing only endogenous IGF-I receptors or overexpressing wild-type IGF-I receptors. The ability of yyFH mutant IGF-I receptors to autophosphorylate the beta-subunit or phosphorylate insulin receptor substrate-1 was not significantly different from wild-type type IGF-I receptors. However, one or both of the proximal tyrosine residues (positions 1250 and 1251) in the carboxy-terminus of the IGF-I receptor are essential for IGF-I-stimulation of mitogenic and tumorigenic pathways. IGF-I-induced mitogenesis, measured as thymidine incorporation and cellular proliferation, was abrogated in cells overexpressing mutant IGF-I receptors with replacement of the proximal double tyrosines (positions 1250 and 1251). Fibroblasts expressing this mutant IGF-I receptor formed fewer tumors than the negative control cells, whereas cells expressing wild-type IGF-I receptors formed large tumors in all recipient mice injected. Conversely, cells expressing mutant IGF-I receptors with only the conserved distal tyrosine (position 1316) replaced had slightly reduced IGF-I-stimulated beta-subunit autophosphorylation, thymidine incorporation, and cellular proliferation when compared with cells expressing wild-type receptors. Phosphorylation of insulin receptor substrate-1 by the yCF mutant receptors was not impaired. Despite the ability of these mutant receptors to stimulate mitogenic growth, fibroblasts expressing this mutant receptor were also incapable of forming tumors in recipient nude mice. The distal tyrosine (position 1316) of the IGF-I receptor is crucial for tumor formation but is not essential for IGF-I stimulated mitogenesis. Thus, the tyrosine moieties in the carboxy-terminus of the IGF-I receptor participate in the signal transduction pathways that affect the mitogenic and tumorigenic potentials of cells expressing mutant IGF-I receptors.

3T3 Cells↗

PubMed1996

Stimulation of endometrial cancer cell growth by tamoxifen is associated with increased insulin-like growth factor (IGF)-I induced tyrosine phosphorylation and reduction in IGF binding proteins.

A significant increase in endometrial cancer incidence in tamoxifen-treated breast cancer patients has been reported in many recent studies. The major growth stimulators of endometrial tumors are estrogens, but paradoxically, tamoxifen, a known antiestrogen, also stimulates their growth. The mode of action of estrogen can be partially explained by the modulation of insulin-like growth factor (IGF) autocrine or paracrine action. The purpose of the present study was to examine the involvement of the IGF system in the tamoxifen-stimulated growth of Ishikawa endometrial cancer cells by quantitating the IGF-I receptors and their phosphorylation, as well as membrane associated and secreted IGF-binding proteins (IGFBPs). Tamoxifen did not affect the number or affinity of IGF-I receptors. On the other hand, tamoxifen, similar to estradiol, increased IGF-I-stimulated tyrosine phosphorylation of cellular substrates. In contrast, in MCF-7 mammary cancer cells, tamoxifen reduced IGF-induced tyrosine phosphorylation in the presence of estradiol. The pure antiestrogen LY156758 did not affect Ishikawa basal cell growth but inhibited estradiol- and tamoxifen-induced growth. Growth inhibition by LY156758 of tamoxifen and estradiol-stimulated cells was accompanied by a corresponding inhibition of IGF-stimulated tyrosine phosphorylation. Tamoxifen caused a 3-fold decrease in membrane-associated IGFBPs. Moreover, a reduction in soluble IGFBPs was also observed, making the IGF peptides more available to the receptors. A parallel decrease in IGFBP-3 mRNA was also detected. These experiments suggest that tamoxifen, like estradiol, directly sensitizes endometrial cancer cells to the effects of IGFs that act through the type I receptor. Furthermore, the decrease in IGFBPs and the increase in tyrosine phosphorylation in the presence of tamoxifen provides a molecular mechanism that accounts for the uterotropic effects that are seen with tamoxifen therapy.

Antineoplastic Agents, Hormonal↗

PubMed1996

A reference cross DNA panel for zebrafish (Danio rerio) anchored with simple sequence length polymorphisms.

The ultimate informativeness of the zebrafish mutations described in this issue will rest in part on the ability to clone these genes. However, the genetic infrastructure required for the positional cloning in zebrafish is still in its infancy. Here we report a reference cross panel of DNA, consisting of 520 F2 progeny (1040 meioses) that has been anchored to a zebrafish genetic linkage map by 102 simple sequence length polymorphisms. This reference cross DNA provides: (1) a panel of DNA from the cross that was used to construct the genetic linkage map, upon which polymorphic gene(s) and genetic markers can be mapped; (2) a fine order mapping tool, with a maximum resolution of 0.1 cM; and (3) a foundation for the development of a physical map (an ordered array of clones each containing a known portion of the genome). This reference cross DNA will serve as a resource enabling investigators to relate genes or genetic markers directly to a single genetic linkage map and avoid the problem of integrating different maps with different genetic markers, as must be currently done when using randomly amplified polymorphic DNA markers, or as has occurred with human genetic linkage maps.

Alleles↗

PubMed1996

Nutritional regulation of insulin-like growth factor-I receptor mRNA levels in growing chickens.

Insulin-like growth factor-I (IGF-I) exerts its effect through the IGF-I receptor. To investigate the effects of nutritional status on chicken IGF-I receptor gene expression, a solution hybridization/RNase protection assay for IGF-I receptor mRNA was developed. A cDNA clone corresponding to the carboxyl-terminal region of the IGF-I receptor was obtained by reverse transcription-PCR (RT-PCR). Sequence analysis of the clone showed that this region of the chicken IGF-I receptor is highly divergent from the human IGF-I receptor. IGF-I receptor mRNA was detected in all tissues examined from newly hatched chickens. The rank order of the IGF-I receptor mRNA levels was liver < thigh muscle < stomach < heart < lung < kidney < brain. In 1-week-old chickens, 5 days of starvation caused a 2.5- to 3-fold increase in the mRNA in muscle and kidney. Starvation of 4-week-old chickens for 5 days caused a 1.7 to 2.2-fold increase in IGF-I receptor mRNA levels in kidney, liver, and muscle. In contrast, IGF-I receptor mRNA levels in brain failed to change. The mRNA levels were reduced to the control level by refeeding of the starved chickens for 24h. These data suggest a tissue- and development-specific response of chicken IGF-I receptor gene expression to nutritional status.

Amino Acid Sequence↗

PubMed1996

Control of insulin-like growth factor (IGF) action by regulation of IGF-I receptor expression.

The insulin-like growth factors (IGFs) control many aspects of growth, development and differentiation, and aberrant IGF action is implicated in a number of pathological states. Most of the actions of both IGF-I and IGF-II are mediated by their activation of the IGF-I receptor, a transmembrane tyrosine kinase that is structurally and functionally related to the insulin receptor. Control of the IGF-I receptor number at the cell surface is an important level at which IGF action can be regulated. Cell-surface receptor number, in turn, is principally determined by the level of expression of the IGF-I receptor gene. An important transcriptional regulatory factor that appears to be responsible for controlling IGF-I receptor gene expression is the product of the WT1 Wilms tumor suppressor gene. This latter protein functions by binding to specific sequences in the IGF-I receptor promoter and repressing transcription. During normal renal development, increased expression of the WT1 gene leads to repression of IGF-I receptor gene expression, allowing differentiation of the metanephrogenic blastema into renal epithelium. Persistent receptor expression due to mutational loss of WT1 function may contribute to the etiology of Wilms tumor. Decreased WT1 expression and subsequent up-regulation of the IGF-I receptor has also been implicated in non-malignant proliferative disorders such as benign prostatic hyperplasia.

DNA-Binding Proteins↗

PubMed1995

The relationship between the index of orthodontic treatment need and consensus opinion of a panel of 74 dentists.

This study looked at the aesthetic and dental health components of the index of orthodontic treatment need in relation to peer assessment of dental health and aesthetic need (panel of 74 dentists). The dental health component had a Spearmans correlation coefficient of +0.64 and the aesthetic component +0.86 when compared with the mean subjective opinion of 74 dentists. It has been proposed to have three categories for both the dental health and aesthetic components in accordance with consensus opinion. The panel of 74 examiners were more likely to regard aesthetics as a greater need for treatment than dental health.

Attitude of Health Personnel↗

PubMed1995

Mutation of a conserved amino acid residue (tryptophan 1173) in the tyrosine kinase domain of the IGF-I receptor abolishes autophosphorylation but does not eliminate biologic function.

The amino acid sequence of the tyrosine kinase domain of the insulin-like growth factor-I (IGF-I) receptor is 84% identical to the sequence of the analogous region of the insulin receptor. A naturally occurring mutation of the tryptophan residue at position 1200 of the insulin receptor to serine results in impaired beta subunit autophosphorylation of wheat germ agglutinin-purified receptors, severely impaired thymidine incorporation and moderately reduced glycogen synthesis; however, glucose uptake was unaffected. To study the importance of this residue in IGF-I receptor function, we mutated the analogous tryptophan residue at position 1173 of the IGF-I receptor to serine and overexpressed the mutant receptor in NIH-3T3 cells. In cell lines overexpressing this mutant IGF-I receptor, beta subunit autophosphorylation was severely reduced. Additionally, the overexpressed mutant receptors exhibited a dominant-negative effect on IGF-I-stimulated autophosphorylation of endogenous mouse IGF-I receptors. Phosphorylation of insulin receptor substrate (IRS)-1 in intact cells by the mutant IGF-I receptors was similar to the level of IRS-1 phosphorylation seen in the parental NIH-3T3 cells, but there was no obvious dominant-negative effect on IRS-1 phosphorylation. Wheat germ agglutinin-purified mutant receptors were as active in phosphorylating poly-(Glu,Tyr) 4:1 as wild-type IGF-I receptors, suggesting that, in intact cells, additional factors are necessary in order for the IGF-I receptor to phosphorylate IRS-1. Thymidine incorporation was severely reduced in one clone overexpressing the mutant IGF-I receptor and abolished in a second clone. Glucose uptake in both clones was reduced to about half of that seen in a cell line over-expressing wild-type IGF-I receptors. Thus, we propose that the tryptophan residue at position 1173 of the IGF-I receptor is important in the regulation of autophosphorylation in vivo. This study again confirms that high levels of autophosphorylation are not required for mediation of all of the biologic activities of the IGF-I receptor.

3T3 Cells↗

PubMed1995

Insulin-like growth factors and cancer.

The insulin-like growth factor (IGF) family of peptides, binding proteins, and receptors are important for normal human growth and development and are involved in the specialized functions of most physiologic systems. Most members of the IGF system are expressed by different cancer cells and may play an important role in the propagation of these malignancies. New therapies aimed at modulating various components of the IGF system could affect the progression and metastasis of cancer.

Animals↗

PubMed1995

Dissociation of mitogenesis and transforming activity by C-terminal truncation of the insulin-like growth factor-I receptor.

We have investigated the mitogenic and transforming ability of an IGF-I receptor with a 108-amino-acid C-terminal truncation in R- cells, which are 3T3-like cells derived from mouse embryos in which the IGF-I receptor genes have been disrupted by targeted homologous recombination. R- cells stably transfected with expression plasmids encoding either a wild-type or a truncated human IGF-I receptor were capable of growing in serum-free medium supplemented solely with IGF-I. This response was observed over a wide range of receptor levels. R- cells overexpressing the wild-type IGF-I receptor also formed colonies in soft agar, and colony formation was augmented by coexpression of the SV40 large T antigen. However, all the examined clones of R- cells expressing the truncated IGF-I receptor exhibited a dramatically impaired ability to grow in soft agar, even in the presence of the T antigen. The inability to form colonies in soft agar was not due to a quantitative impairment of signal transduction, because: (1) SV40-transformed cells with a physiological level of the wild-type IGF-I receptor did not respond to IGF-I with cell proliferation, but grew in soft agar; (2) R- cells stably transfected with both a truncated receptor and T antigen, on the contrary, responded with mitogenesis to IGF-I but could not form colonies in soft agar; (3) some clones with the truncated receptor expressed levels of receptor roughly 100-fold the level of wild-type cells; and (4) several parameters of IGF-I receptor signal transduction were not impaired in cells stably transfected with a truncated receptor. Furthermore, overexpression of an activated ras in cells with the truncated IGF-IR did not restore their ability to proliferate under anchorage-independent conditions. We conclude that the 108 amino acids of the IGF-I receptor are not essential for a mitogenic response to IGF-I, but are required for transformation (as assessed by the ability to grow in soft agar), indicating that these two functions can be dissociated at an intramolecular level. Moreover, although ras (activated) certainly plays a role in transformation, the transforming activity of the IGF-IR also requires signaling elements that are ras-dependent.

3T3 Cells↗