scholarly journals Constitutive phosphorylation of the receptor for insulinlike growth factor I in cells transformed by the src oncogene.

1990 ◽  
Vol 10 (7) ◽  
pp. 3626-3634 ◽  
Author(s):  
L M Kozma ◽  
M J Weber
Keyword(s):  
Growth Factor ◽  
Beta Subunit ◽  
Transformed Cells ◽  
Receptor Phosphorylation ◽  
Factor I ◽  
Insulinlike Growth Factor ◽  
Igf I ◽  
Growth Factor I ◽  
Insulinlike Growth Factor I ◽  
In Cells

Many oncogene products have been shown to bear strong homology to or to interact with components of normal cellular signal transduction. We have previously shown that a glycoprotein band of 95 kilodaltons (kDa) becomes tyrosine phosphorylated in chick cells transformed by Rous sarcoma virus and that tyrosine phosphorylation of this protein band correlates tightly with phenotypic transformation in cells infected with a large and diverse panel of src mutants (L. M. Kozma, A. B. Reynolds, and M. J. Weber, Mol. Cell. Biol. 10:837-841, 1990). In this communication, we report that a component of the 95-kDa glycoprotein band is related or identical to the 95-kDa beta subunit of the receptor for insulinlike growth factor I (IGF-I). We found that the beta subunit of the IGF-I receptor comigrated on polyacrylamide gels with a component of the 95-kDa glycoprotein region from src-transformed cells under both reducing and nonreducing gel conditions and had a very similar partial phosphopeptide map. To further test the hypothesis that the beta subunit of the IGF-I receptor becomes tyrosine phosphorylated in cells transformed by pp60src, a human cell line that expressed the IGF-I receptor was transformed by src. Comparison of IGF-I receptors immunoprecipitated from normal and transformed cells revealed that the beta subunit of the IGF-I receptor became constitutively tyrosine phosphorylated in src-transformed cells. Moreover, IGF-I receptor phosphorylation induced by src was synergistic with that induced by the hormone: IGF-I-stimulated autophosphorylation of the receptor was much greater in src-transformed cells than in untransformed HOS cells even at maximal concentrations of IGF-I. This increased responsiveness to IGF-I was not due to increases in receptor number, time course of phosphorylation, or affinity for hormone. Finally, no IGF-I-like activity could be detected in culture supernatants collected from the src-transformed cells, suggesting that the increased receptor phosphorylation observed in the src-transformed cells may be mediated by an intracellular mechanism rather than an external autocrine stimulation. Our data demonstrate that the IGF-I receptor becomes constitutively tyrosine phosphorylated in src-transformed cells. This finding raises the possibility that pp60v-src alters growth regulation at least in part by phosphorylating and activating this growth factor receptor.

Constitutive phosphorylation of the receptor for insulinlike growth factor I in cells transformed by the src oncogene

1990 ◽  
Vol 10 (7) ◽  
pp. 3626-3634
Author(s):  
L M Kozma ◽  
M J Weber
Keyword(s):  
Growth Factor ◽  
Beta Subunit ◽  
Transformed Cells ◽  
Receptor Phosphorylation ◽  
Factor I ◽  
Insulinlike Growth Factor ◽  
Igf I ◽  
Growth Factor I ◽  
Insulinlike Growth Factor I ◽  
In Cells

Many oncogene products have been shown to bear strong homology to or to interact with components of normal cellular signal transduction. We have previously shown that a glycoprotein band of 95 kilodaltons (kDa) becomes tyrosine phosphorylated in chick cells transformed by Rous sarcoma virus and that tyrosine phosphorylation of this protein band correlates tightly with phenotypic transformation in cells infected with a large and diverse panel of src mutants (L. M. Kozma, A. B. Reynolds, and M. J. Weber, Mol. Cell. Biol. 10:837-841, 1990). In this communication, we report that a component of the 95-kDa glycoprotein band is related or identical to the 95-kDa beta subunit of the receptor for insulinlike growth factor I (IGF-I). We found that the beta subunit of the IGF-I receptor comigrated on polyacrylamide gels with a component of the 95-kDa glycoprotein region from src-transformed cells under both reducing and nonreducing gel conditions and had a very similar partial phosphopeptide map. To further test the hypothesis that the beta subunit of the IGF-I receptor becomes tyrosine phosphorylated in cells transformed by pp60src, a human cell line that expressed the IGF-I receptor was transformed by src. Comparison of IGF-I receptors immunoprecipitated from normal and transformed cells revealed that the beta subunit of the IGF-I receptor became constitutively tyrosine phosphorylated in src-transformed cells. Moreover, IGF-I receptor phosphorylation induced by src was synergistic with that induced by the hormone: IGF-I-stimulated autophosphorylation of the receptor was much greater in src-transformed cells than in untransformed HOS cells even at maximal concentrations of IGF-I. This increased responsiveness to IGF-I was not due to increases in receptor number, time course of phosphorylation, or affinity for hormone. Finally, no IGF-I-like activity could be detected in culture supernatants collected from the src-transformed cells, suggesting that the increased receptor phosphorylation observed in the src-transformed cells may be mediated by an intracellular mechanism rather than an external autocrine stimulation. Our data demonstrate that the IGF-I receptor becomes constitutively tyrosine phosphorylated in src-transformed cells. This finding raises the possibility that pp60v-src alters growth regulation at least in part by phosphorylating and activating this growth factor receptor.

Serum Ghrelin Concentrations are Increased in Children With Growth Hormone Insensitivity and Decrease During Long-Term Insulinlike Growth Factor-I Treatment

2008 ◽  
Vol 56 (1) ◽  
pp. 26-31 ◽  
Author(s):  
Aysin Uckun-Kitapci ◽  
Andrea M. Haqq ◽  
Jonathan Q. Purnell ◽  
Kenneth Newcomb ◽  
Hakan Gulkesen ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Normal Control ◽  
Blood Draw ◽  
Gh Secretion ◽  
Factor I ◽  
Insulinlike Growth Factor ◽  
Igf I ◽  
Growth Factor I ◽  
Insulinlike Growth Factor I

BackgroundGhrelin increases food intake, body weight, and growth hormone (GH) secretion. Serum concentrations of ghrelin are low in obese hyperinsulinemic persons, are reduced by infusion of insulin into normal-weight subjects, and are increased in underweight hypoinsulinemic patients with anorexia nervosa. Laron syndrome is an autosomal recessive disorder of GH insensitivity that results in decreased insulinlike growth factor-I (IGF-I) synthesis and growth failure. These patients have elevated GH levels, excess adipose tissue, and are insulin resistant. Because IGF-I has insulinlike actions and patients with GH insensitivity syndrome (GHIS) exhibit excess adiposity, we sought to determine whether ghrelin levels were elevated in these patients and potentially regulated by IGF-I replacement.MethodsThirteen children with GHIS and 20 normal control children matched for age, sex, and body mass index underwent complete physical examination and a fasting blood draw at baseline. The GHIS subjects then underwent follow-up fasting blood draws during therapy with human recombinant IGF-I (80-120 μg/kg, given subcutaneously twice daily). Fasting glucose, insulin, and IGF-I concentrations were measured at the time of collection. Fasting total ghrelin levels were measured on stored serum samples.ResultsThe GHIS subjects had 2-fold higher fasting ghrelin levels (2926 ± 1869 pg/mL) compared with the normal control children (1492 ± 493 pg/mL; P = 0.009), and mean ghrelin values were reduced 56% during 6.4 ± 0.2 years of IGF-I replacement (P < 0.05).ConclusionsGrowth hormone resistance and low IGF-I levels are associated with elevated ghrelin levels, which may potentiate GH secretion and adiposity in these children. Suppression of ghrelin during IGF-I treatment suggests a novel mechanism potentially regulating ghrelin levels.

Somatomedin C/insulinlike growth factor I during liver regeneration in the rat

1985 ◽  
Vol 248 (5) ◽  
pp. E618-E623 ◽  
Author(s):  
W. E. Russell ◽  
A. J. D'Ercole ◽  
L. E. Underwood
Keyword(s):  
Growth Factor ◽  
Liver Regeneration ◽  
Mean Value ◽  
Hepatocellular Injury ◽  
Somatomedin C ◽  
Factor I ◽  
Insulinlike Growth Factor ◽  
Igf I ◽  
Growth Factor I ◽  
Insulinlike Growth Factor I

We measured immunoreactive somatomedin C/insulinlike growth factor I (Sm C/IGF I) in blood and tissues of rats following partial hepatectomy (PH) to determine a possible regulatory role for this growth factor in liver regeneration. From a mean value of 0.66 U/ml +/- 0.19 before PH, the serum Sm C/IGF I rose to 1.09 +/- 0.08 1 h after PH [P less than 0.001 vs. sham-hepatectomized (SH) values]. Concurrently there was a twofold rise in serum aspartate aminotransferase, suggesting that the rise in Sm C/IGF I may be the result of hepatocellular injury rather than a specific secretory event. In the subsequent 22 h, serum Sm C/IGF I of PH rats fell to 0.31 +/- 0.06 U/ml, compared with 0.73 +/- 0.03 in SH rats. During this time, liver concentrations of the peptide declined to 30% of basal, whereas lung and kidney fell to only approximately 60% of basal. As the Sm C/IGF I declined, hepatic DNA synthesis increased 10-fold in PH animals. Our results, therefore, do not support a mitogenic role for Sm C/IGF I in the regulation of liver regulation. Food consumption was markedly depressed in the 22 h after PH (20.8 +/- 2.6 vs. 4.33 +/- 2.9 g/day; P less than 0.001). PH and pair-fed SH rats had serum Sm C/IGF I concentrations that were indistinguishable (0.31 +/- 0.06 vs. 0.35 +/- 0.11 U/ml), although liver tissue concentrations were lower in PH rats (0.04 +/- 0.01 U/g vs. 0.07 +/- 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic treatment with insulinlike growth factor-I (IGF-I) causes growth of the prostate in the rat

1996 ◽  
Vol 64 (1-3) ◽  
pp. 193
Author(s):  
Niels Tørring ◽  
Lars Vinter Jensen ◽  
Allan Flyvbjerg ◽  
Steen Bønløkke Pedersen ◽  
Flemming Brandt Sørensen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Systemic Treatment ◽  
Factor I ◽  
Insulinlike Growth Factor ◽  
Igf I ◽  
Growth Factor I ◽  
Insulinlike Growth Factor I

Activation of the ribosomal DNA promoter in cells exposed to insulinlike growth factor I

1987 ◽  
Vol 7 (2) ◽  
pp. 657-663
Author(s):  
E Surmacz ◽  
L Kaczmarek ◽  
O Rønning ◽  
R Baserga
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Ribosomal Dna ◽  
T Antigen ◽  
Platelet Poor Plasma ◽  
Factor I ◽  
Insulinlike Growth Factor ◽  
Igf I ◽  
Growth Factor I ◽  
Insulinlike Growth Factor I

We constructed a stable cell line, 3T3A5, which carried a chimeric gene in which the simian virus 40 T-antigen-coding gene was under the control of the mouse ribosomal DNA promoter. These cells expressed T antigen when they were growing exponentially in 10% fetal calf serum, but they all became T negative when incubated for 5 days in low-concentration serum. The readdition of serum or platelet-poor plasma again induced the expression of T antigen, which was accompanied by an increase in steady-state levels of the corresponding RNA. Among the various growth factors tested for their ability to induce T-antigen expression in 3T3A5 cells, only insulinlike growth factor I (IGF-I) could induce T antigen at physiological concentrations. The effect of IGF-I or platelet-poor plasma was abolished by an antibody to IGF-I. Other growth factors, like insulin and epidermal growth factor, could induce the expression of T antigen in 3T3A5 cells, but only at concentrations far above the physiological range. Other growth factors were totally ineffective. These results indicate that exposure of cells to IGF-I can activate transcription from the ribosomal DNA promoter.

scholarly journals Activation of the ribosomal DNA promoter in cells exposed to insulinlike growth factor I.

1987 ◽  
Vol 7 (2) ◽  
pp. 657-663 ◽  
Author(s):  
E Surmacz ◽  
L Kaczmarek ◽  
O Rønning ◽  
R Baserga
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Ribosomal Dna ◽  
T Antigen ◽  
Platelet Poor Plasma ◽  
Factor I ◽  
Insulinlike Growth Factor ◽  
Igf I ◽  
Growth Factor I ◽  
Insulinlike Growth Factor I

We constructed a stable cell line, 3T3A5, which carried a chimeric gene in which the simian virus 40 T-antigen-coding gene was under the control of the mouse ribosomal DNA promoter. These cells expressed T antigen when they were growing exponentially in 10% fetal calf serum, but they all became T negative when incubated for 5 days in low-concentration serum. The readdition of serum or platelet-poor plasma again induced the expression of T antigen, which was accompanied by an increase in steady-state levels of the corresponding RNA. Among the various growth factors tested for their ability to induce T-antigen expression in 3T3A5 cells, only insulinlike growth factor I (IGF-I) could induce T antigen at physiological concentrations. The effect of IGF-I or platelet-poor plasma was abolished by an antibody to IGF-I. Other growth factors, like insulin and epidermal growth factor, could induce the expression of T antigen in 3T3A5 cells, but only at concentrations far above the physiological range. Other growth factors were totally ineffective. These results indicate that exposure of cells to IGF-I can activate transcription from the ribosomal DNA promoter.

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