The role of human
prostatic acid phosphatase (PAcP, P15309|
PPAP_HUMAN) in
prostate cancer was investigated using a new proteomic tool termed
signal sequence swapping (replacement of domains from the native cleaved amino terminal
signal sequence of secretory/
membrane proteins with corresponding regions of functionally distinct
signal sequence subtypes). This manipulation preferentially redirects
proteins to different pathways of biogenesis at the endoplasmic reticulum, magnifying normally difficult to detect subsets of the
protein of interest. For PAcP this technique reveals three forms identical in amino acid sequence but profoundly different in physiological functions, subcellular location, and biochemical properties. These three forms of PAcP can also occur with the wild-type PAcP
signal sequence. Clinical specimens from patients with
prostate cancer demonstrate that one form, termed PLPAcP, correlates with early
prostate cancer. These findings confirm the analytical power of this method, implicate PLPAcP in
prostate cancer pathogenesis, and suggest novel anticancer therapeutic strategies.