Glucose transporter vesicle aminopeptidase

Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Hydrolase

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435212, 435226, 435325, 4352523, 43525233, 4353201, 536 231, 536 232, 536 235, C12N 950, C07H 2104

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active

059726806

ABSTRACT:
An aminopeptidase which is a component of GLUT4-containing vesicles in the natural state, and which cleaves insulin. The claimed protein has an apparent molecular weight of approximately 110 kD in its deglycosylated form and a predicted molecular weight of 117,239 Daltons. It includes the amino acid sequences Phe-Ala-Ala-Thr-Gln-Phe-Glu-Pro-Leu-Ala-Ala (SEQ ID NO: 1) and Ile-Leu-Gln-Asn-Gln-Ile-Gln-Gln-Gln-Thr-Arg-Thr-Asp-Glu-Gly-Xaa-Pro-Xaa-Me t (SEQ ID NO: 2, and reacts with antibodies produced against the peptide identified as (SEQ ID NO: 1). It is encoded by the cDNA of FIG. 20 (SEQ. ID NOs. 15 and 16) and is essentially the protein sequence therein described. Modulators of the activity of the aminopeptidase and a method for treating syndromes of insulin resistance, including diabetes, by administration of such a modulator are also claimed.

REFERENCES:
Kandror et al. "Identification and isolation of glycprotein that translocate to the cell surface from GLUT4-enriched vesicle in an insulin-dependent fashion" J. Biol. Chem. 269, 138-142, Jan. 1994.
Mastick et al. "Characterization of a major protein in GLUT4 vesicles" J. Biol. Chem. 269, 6089-6092, Feb. 1994.
Kandror et al. "gp160, a tissue-specific marker for insulin-activated gklucose transport" Proc. Natl. Acad. Sci. USA 91, 8017-8021, Aug. 1994.
Rogi et al. "Human placental leucine aminopeptidase/oxytocinase" J. Biol. Chem. 271, 56-61, Jan. 1996.
Keller et al. "Cloning and characterization of a novel insulin-regulated membrane aminopeptidase from Glut vesicles" J. Biol. Chem. 270, 23612-23618, Oct. 1995.
James, D., et al, Letters to Nature, 338, 83-87, (1989).
Verhey, K. et al, J. Biol., Chem., 269, 2353-2356 (1994).
Tsujimoto, M. et al, Archives of Biochem and BioPhys. 292, 388-392 (1992).
Kandror, et al., "The Major Protein of GLUT4-containing Vesicles, gp160, Has Aminopeptidase Activity", J. Biol. Chem., 269:49, pp. 30777-30780 (Dec. 9, 1994).

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