Identification of a novel structural variant of the α6 integrin

The alpha P-6 integrin is a 140-kDa (nonreduced) laminin receptor. We have identified a novel 70-kDa (nonreduced) form of the alpha (6) integrin called alpha P-6 for the latin word parvus, meaning small. The variant was immunoprecipitated from human cells using four different alpha (6)-specific monoclonal antibodies but not with alpha (3) or alpha (5) antibodies. The alpha P-6 integrin contained identical amino acid sequences within exons 13-25, corresponding to the extracellular "stalk region" and the cytoplasmic tail of the alpha (6) integrin. The light chains of alpha P-6 and alpha P-6 were identical as judged by alpha (6)A-specific antibodies and electrophoretic properties. The alpha P-6 variant paired with either beta (1) or beta (4) subunits and was retained on the cell surface three times longer than alpha (6). Reverse transcription/polymerase chain reaction analysis revealed a single polymerase chain reaction product. The alpha P-6 variant was found in human prostate (DU145H, LnCaP, PC3) and colon (SW480) cancer cell lines but not in normal prostate (PrEC), breast cancer (MCF-7), or lung cancer (H69) cell lines or a variant of a prostate carcinoma cell line (PC3-N), Protein levels of alpha P-6 increased 3-fold during calcium-induced terminal differentiation in a normal mouse keratinocyte model system. A novel form of the alpha (6) integrin exists on cell surfaces that contains a dramatically altered extracellular domain.