Center of Mass Calculation in Combination with MS/MS Allows Robust Identification of Single Amino Acid Polymorphisms in Clinical Measurements of Insulin-Like Growth Factor-1

2019 ◽  
Vol 19 (1) ◽  
pp. 186-193 ◽  
Author(s):  
Anthony Maus ◽  
Jennifer Kemp ◽  
Dragana Milosevic ◽  
Santosh Renuse ◽  
Akhilesh Pandey ◽  
...  
Keyword(s):  
Amino Acid ◽  
Growth Factor ◽  
Center Of Mass ◽  
Single Amino Acid ◽  
Insulin Like Growth Factor ◽  
Robust Identification ◽  
Single Amino Acid Polymorphisms ◽  
Clinical Measurements

scholarly journals Transforming growth factor alpha: mutation of aspartic acid 47 and leucine 48 results in different biological activities.

1988 ◽  
Vol 8 (3) ◽  
pp. 1247-1252 ◽  
Author(s):  
E Lazar ◽  
S Watanabe ◽  
S Dalton ◽  
M B Sporn
Keyword(s):  
Amino Acids ◽  
Biological Activity ◽  
Amino Acid ◽  
Growth Factor ◽  
Aspartic Acid ◽  
Transforming Growth Factor ◽  
Biologically Active ◽  
Single Amino Acid ◽  
Transforming Growth Factor Alpha ◽  
Factor Alpha

To study the relationship between the primary structure of transforming growth factor alpha (TGF-alpha) and some of its functional properties (competition with epidermal growth factor (EGF) for binding to the EGF receptor and induction of anchorage-independent growth), we introduced single amino acid mutations into the sequence for the fully processed, 50-amino-acid human TGF-alpha. The wild-type and mutant proteins were expressed in a vector by using a yeast alpha mating pheromone promoter. Mutations of two amino acids that are conserved in the family of the EGF-like peptides and are located in the carboxy-terminal part of TGF-alpha resulted in different biological effects. When aspartic acid 47 was mutated to alanine or asparagine, biological activity was retained; in contrast, substitutions of this residue with serine or glutamic acid generated mutants with reduced binding and colony-forming capacities. When leucine 48 was mutated to alanine, a complete loss of binding and colony-forming abilities resulted; mutation of leucine 48 to isoleucine or methionine resulted in very low activities. Our data suggest that these two adjacent conserved amino acids in positions 47 and 48 play different roles in defining the structure and/or biological activity of TGF-alpha and that the carboxy terminus of TGF-alpha is involved in interactions with cellular TGF-alpha receptors. The side chain of leucine 48 appears to be crucial either indirectly in determining the biologically active conformation of TGF-alpha or directly in the molecular recognition of TGF-alpha by its receptor.

scholarly journals Amino acid regulation of gene transcription of rat insulin-like growth factor-binding protein-1

2000 ◽  
Vol 164 (3) ◽  
pp. R11-R16 ◽  
Author(s):  
A Takenaka ◽  
K Komori ◽  
T Morishita ◽  
SI Takahashi ◽  
T Hidaka ◽  
...  
Keyword(s):  
Amino Acid ◽  
Growth Factor ◽  
Gene Transcription ◽  
Binding Protein ◽  
Present Observation ◽  
Insulin Like Growth Factor ◽  
Amino Acid Deprivation ◽  
Cis Acting ◽  
Factor Binding ◽  
Responsive Element

To investigate the molecular mechanisms of increased transcription of the insulin-like growth factor-binding protein-1 (IGFBP-1) gene in dietary protein-deprived animals, the cis-acting sequence that is involved in this regulation was analyzed. We first showed that IGFBP-1 gene transcription was up-regulated by amino acid deprivation in cultured liver cell lines: H4IIE and HuH-7. Since HuH-7 cells showed a greater increase in IGFBP-1 mRNA in response to amino acid deprivation, this cell line was used in further experiments. Using a promoter function assay, we found that up-regulation of promoter activity responding to amino acid deprivation was abolished by deleting the region between -112 and -81 bp from the cap site from the gene construct. This cis-acting region includes the insulin-responsive element (IRE) and glucocorticoid responsive element (GRE) of IGFBP-1. In summary, the present observation suggests that the 32-bp (-112 to -81) in the IGFBP-1 gene 5' promoter region is involved in the induction of the IGFBP-1 gene in response to amino acid deprivation.

scholarly journals Effect of single amino acid substitutions on the formation of the PlA and Bak alloantigenic epitopes

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 681-687 ◽  
Author(s):  
A Goldberger ◽  
M Kolodziej ◽  
M Poncz ◽  
JS Bennett ◽  
PJ Newman
Keyword(s):  
Amino Acid ◽  
Expression System ◽  
Single Amino Acid ◽  
Expression Vectors ◽  
Membrane Glycoproteins ◽  
Amino Acid Polymorphism ◽  
Specific Expression ◽  
Mammalian Expression ◽  
Single Amino Acid Polymorphisms ◽  
Necessary And Sufficient

Abstract The subunits that comprise the platelet-specific integrin alpha IIb beta 3 are polymorphic in nature, with several allelic forms present in the human gene pool. Minor changes in the secondary and tertiary structures of platelet membrane glycoproteins (GP) IIb and IIIa encoded by these alleles can result in an alloimmune reaction after transfusion or during pregnancy. To better understand the molecular structure of the PlA alloantigen system, located on GPIIIa, and the Bak alloantigen on GPIIb, we used a heterologous mammalian expression system to express these integrin subunits in their known polymorphic forms. An expression vector containing the PlA1 form of a GPIIIa cDNA, which encodes a leucine at amino acid 33 (Leu33), was modified to express the PlA2- associated form encoding a proline at amino acid 33 (Pro33). Similarly, a Baka GPIIb cDNA expressing an isoleucine at amino acid 843 (IIe843) was modified to express the Bakb form containing a serine at the same position (Ser843). Transfection of these vectors into COS cells resulted in the synthesis of GPIIb and GPIIIa molecules that were identical in size to those present in platelet lysates. Immunoprecipitation of the GPIIIa-transfected COS lysates with PlA)- specific alloantisera indicated that the Leu33 form was recognized only by anti-PIA1 sera while the Pro33 form was bound only by anti-PlA2 sera, showing that single amino acid polymorphisms are necessary and sufficient to direct the formation of the PlA1 and PlA2 alloepitopes. Similar experiments with Bak allele-specific expression vectors indicated that while the amino acid polymorphism (IIe843 in equilibrium Ser843) was necessary, posttranslational processing of pro-IIb was required for efficient exposure of both the Baka and Bakb alloepitopes.

Effects of insulin, insulin-like growth factor-I (IGF-I) and progesterone on glucose and amino acid uptake in Xenopus laevis oocytes

1991 ◽  
Vol 75 (2) ◽  
pp. 133-139 ◽  
Author(s):  
Pierre Hainaut ◽  
Aline Kowalski ◽  
Yannick Le Marchand-Brustel ◽  
Sophie Giorgetti ◽  
Nadine Gautier ◽  
...  
Keyword(s):  
Amino Acid ◽  
Growth Factor ◽  
Xenopus Laevis ◽  
Amino Acid Uptake ◽  
Xenopus Laevis Oocytes ◽  
Acid Uptake ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I
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