Phosphorylation of Amyloid Precursor Protein (APP) Family Proteins

It has been well established that β-amyloid peptide is the principal protein component of extracellular cerebral amyloid deposits in patients with Alzheimer's disease (1,2). β-Amyloid is derived from a large precursor protein, amyloid precursor protein (APP), which is an integral membrane protein, with a receptor-like structure (3). APP is a member of a gene family which encodes extremely well-conserved membrane proteins. APP/APP-like genes have been isolated from various species including fly (4), nematode (5), and fish (6). In mammals, two APP-like genes, amyloid precursor-like protein 1 (APLP1) and 2 (APLP2), have been isolated (7,8). The amino acid sequences of these APP family proteins are highly conserved, especially in the cytoplasmic domain, except that unlike APP, APP-like proteins lack the β-amyloid sequence. It has been thought that APP and APLP2 have a similar physiological function (9). In contrast, APLP1 is believed to differ functionally from APP and APLP2, although the physiological functions of these APP family proteins have not yet been well analyzed.