A family of membrane proteins associated with presenilin expression and gamma-secretase function.

Presenilin 1 (PS1) forms the gamma-secretase complex with at least three components: nicastrin, APH-1, and PEN-2. This complex mediates intramembrane cleavage of amyloid precursor protein (APP) to generate beta-amyloid protein (Abeta) as well as other type 1 transmembrane proteins. Although PS1 mutations linked to familial Alzheimer's disease influence these cleavages, their biological consequences have not been fully understood.

Characterization of APH-1 mutants with a disrupted transmembrane GxxxG motif.

APH-1 is one of the four essential components of presenilin (PS)-gamma-secretase complexes. There are three major isoforms of APH-1 in humans: APH-1aS, APH-1aL, and APH-1b. To gain insight into the functional role of APH-1 in gamma-secretase complexes, we analyzed the relationship between the three APH-1 forms and characterized APH-1 mutants with a disrupted transmembrane GxxxG motif.

Ribozymes targeting serine/threonine kinase Akt1 sensitize cells to anticancer drugs.

The serine/threonine kinase Akt is a key component of the cellular signaling pathway for survival and drug-resistance in cancer cells. In the present study we confirmed this view by expressing an antagonist of Akt, a dominant negative form of Akt, in HCT116 colon carcinoma cells and observing apoptosis induction in cells in which expression of the mutant protein had been induced. Three isoforms of Akt have been found: Akt1/PKBalpha, Akt2/PKBbeta and Akt3/PKBgamma.

Identification and characterization of a novel human APH-1b splice variant lacking exon 4.

APH-1 is one of the four essential components of the presenilin-gamma-secretase complex and has two human homologs, APH-1a, and APH-1b, both of which are seven-pass membrane proteins. Here, we identified a novel splice variant of human APH-1b. This variant lacks exon 4, which encodes the entire fourth transmembrane domain.