Characterization of human foetal intestinal alkaline phosphatase. Comparison with the isoenzymes from the adult intestine and human tumour cell lines

Abstract

The molecular structure of human foetal intestinal alkaline phosphatase was defined by high-resolution two-dimensional polyacrylamide-gel electrophoresis and amino acid inhibition studies. Comparison was made with the adult form of intestinal alkaline phosphatase, as well as with alkaline phosphatases isolated from cultured foetal amnion cells (FL) and a human tumour cell line (KB). Two non-identical subunits were isolated from the foetal intestinal isoenzyme, one having same molecular weight and isoelectric point as placental alkaline phosphatase, and the other corresponding to a glycosylated subunit of the adult intestinal enzyme. The FL-cell and KB-cell alkaline phosphatases were also found to contain two subunits similar to those of the foetal intestinal isoenzyme. Characterization of neuraminidase digests of the non-placental subunit showed it to be indistinguishable from the subunits of the adult intestinal isoenzyme. This implies that no new phosphatase structural gene is involved in the transition from the expression of foetal to adult intestinal alkaline phosphatase, but that the molecular changes involve suppression of the placental subunit and loss of neuraminic acid from the non-placental subunit. Enzyme-inhibition studies demonstrated an intermediate response to the inhibitors tested for the foetal intestinal, FL-cell and KB-cell isoenzymes when compared with the placental, adult intestinal and liver forms. This result is consistent with the mixed-subunit structure observed for the former set of isoenzymes. In summary, this study has defined the molecular subunit structure of the foetal intestinal form of alkaline phosphatase and has demonstrated its expression in a human tumour cell line.

Placental and intestinal alkaline phosphatases are receptors for Aeromonas sobria hemolysin

“…Heterodimers can also form in normal tissues with heterodimeric forms of PLAP and IAP having been reported in the human intestine (Behrens et al, 1983). Both the EAP (the mouse ortholog of human PLAP) and the IAP genes are expressed in the mouse intestine (Hahnel et al, 1990).…”

“…While PLAP has been reported to be expressed in the neonatal intestine (Behrens et al, 1983), it is not clear if PLAP is also found in the adult intestine. To examine PLAP expression on human mucosa specimens, we performed an immunohistochemical analysis using an anti-PLAP antibody.…”

“…In addition, we find that the homologous, intestinal alkaline phosphatase (IAP) isozyme, also served as an A. sobria hemolysin receptor. Since both PLAP and IAP are co-expressed in the neonatal intestine (Behrens et al, 1983), these molecules are very likely involved in the pathogenesis of diarrhea caused by this bacterial toxin.…”

Expression and characterization of alkaline phosphatases during differentiation of human pancreatic cancer (Capan‐1) cells in culture

“…They are classified according to their tissue distribution into an intestinal, a placental and a liver/bone/kidney type [33]. A placental-like [24] and fetal intestinal [6] type have also been described. AP have generally been considered to be homodimers, but recent work has suggested that the liver/bone/kidney type is in fact tetrameric [17].…”

A Hybrid Form of Alkaline Phosphatase Produced in FL-Amnion Cells

“…On the other hand, the other slower migrating AP isozyme (FL-APs) in FL-amnion cells has not yet been characterized. Behrens et al [5] reported that AP in FL-amnion cells con sisted of two distinct subunits, one coming from placental AP and another one from fetal intestinal AP. They also showed that a neuraminidase digest of the nonplacental subunits is indistinguishable from the sub unit of the adult intestinal isozyme.…”