Proteins that bind to the RERMS region of beta amyloid precursor protein.
The main objective of this study was to investigate the biological function of beta amyloid precursor protein (APP), in particular its nerve growth factor-like activity. We hypothesize that the extracellular domain containing the sequence RERMS, amino acids 328-332 of APP(695), represents the active site for this function. Binding assays using peptide fragments of this domain have demonstrated specific and saturable binding to the cell surface with affinity in the low nanomolar range. This induced our quest for an APP-specific receptor. We chose different peptide fragments of the RERMS domain as ligands and displacing agents on affinity columns to purify APP-binding molecules. Amino acid microsequencing yielded partial sequences of serum albumin, actin, two novel proteins of 41 and 63kDa, and human Collapsin Response Mediator Protein-2 (hCRMP-2). Because both APP and hCRMP-2 promote neuronal outgrowth and use a common signaling pathway, APP could be acting through a semaphorin receptor as well.
Pawlik
Monika
M
Nathan Kline Institute, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA. MPawlik@nki.rfmh.org
Otero
Deborah A C
DA
Park
Minkyu
M
Fischer
Wolfgang H
WH
Levy
Efrat
E
Saitoh
Tsunao
T
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D020816:Amino Acid Motifs; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D020355:Cholates; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011485:Protein Binding; D013552:Swine
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D016564:Amyloid beta-Protein Precursor; D020355:Cholates; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C095114:collapsin response mediator protein-2