Ligand-dependent G Protein Coupling Function of Amyloid Transmembrane Precursor (*)

  1. Ikuo Nishimoto(1)(§)
  1. From the (1)Cardiovascular Research Center, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Charlestown, Massachusetts 02129, the
  2. (2)Fourth Department of Internal Medicine, Tokyo University School of Medicine, 3-28-6 Mejirodai, Bunkyo-ku, Tokyo 112, Japan, and the
  3. (3)Cancer Research Institute, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170, Japan
  1. § To whom correspondence should be addressed: Cardiovascular Research Center, Massachusetts General Hospital and Dept. of Medicine, Harvard Medical School, 149 13th St., Charlestown, MA 02129. Tel.: 617-726-4348; Fax: 617-726-5806; nishimoto{at}


Amyloid precursor protein (APP), a transmembrane precursor of β-amyloid, possesses a function whereby it associates with Go through its cytoplasmic His657-Lys676. Here we demonstrate that APP has a receptor function. In phospholipid vesicles consisting of baculovirally made APP695 and brain trimeric Go, 22C11, a monoclonal antibody against the extracellular domain of APP, increased GTPγS binding and the turnover number of GTPase of Go without affecting its intrinsic GTPase activity. This effect of 22C11 was specific among various antibodies and was observed neither in Go vesicles nor in APP695/Go vesicles. In APP695/Go vesicles, synthetic APP66−81, the epitope of 22C11, competitively antagonized the action of 22C11. Monoclonal antibody against APP657−676, the Go binding domain of APP695, specifically blocked 22C11-dependent activation of Go. Therefore, APP has a potential receptor function whereby it specifically activates Go in a ligand-dependent and ligand-specific manner.


  • * This work was supported in part by Bristol-Myers Squibb and by grants from the Ministry of Education, Science, and Culture of Japan, Chugai, and Hoechst. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

  • Received November 11, 1994.
  • Revision received January 4, 1995.
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