Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene for insulin-like growth factor I (IGF-I) was constructed from chemically synthesized deoxyoligonucleotides and expressed in Escherichia coli, under the control of a trp promoter, as a set of fusion proteins which were connected with a portion of human growth hormone through the recognition sequence for a sequence-specific protease, either blood coagulation factor Xa or alpha-thrombin. Upon induction with 3-indoleacrylic acid, fusion proteins accumulated with a yield of 10-30% of the total protein. A fusion protein connected through a tetradecapeptide (Asp-Asp-Pro-Pro-Thr-Val-Glu-Leu-Gln-Gly-Leu-Val-Pro-Arg) was efficiently and correctly cleaved by alpha-thrombin, and the purified IGF-I possessed somatomedin-like activity, as determined by the enhancement of sulfation of glycosaminoglycans in cultured costal chondrocytes from rabbits.
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PMID:Efficient cleavage by alpha-thrombin of a recombinant fused protein which contains insulin-like growth factor I. 333

We have displayed insulin-like growth factor I (IGF-I) as an N-terminal extension of 4070A (amphotropic) retroviral envelope protein. Western blot demonstrated that chimaeric envelope proteins were incorporated into retroviral particles. Interaction between the displayed IGF-I and cell-surface receptors impaired gene delivery. The magnitude of this inhibitory effect was smallest on NIH 3T3 cells, greater on NIH 3T3 cells over-expressing insulin receptor, and greatest on NIH 3T3 cells over-expressing human type-I IGF receptor. Hence, both the number of ligand receptors and their affinity for the displayed ligand influenced the level of gene delivery. The inhibitory effect was abrogated by cleaving the displayed domain from the underlying envelope protein with factor Xa protease, and by the addition of free ligand to the infection. Addition of IGF-I or insulin caused a dose-dependent increase in titre. Possible mechanisms for receptor-mediated inhibition of gene delivery by IGF-displaying vectors are discussed, together with the implications of these results for practical applications of retroviral display and for understanding the mechanism of virus entry.
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PMID:Modification of retroviral tropism by display of IGF-I. 987 23