Popis: |
Phosphatidic acid (PA) and diacylglycerol (DG) are lipids involved in signal transduction and in structural membrane lipid biosynthesis in cells. Phosphatidic acid phosphatase (PAP) (EC 3.1.3.4) catalyzes the conversion of PA to DG. This enzyme is known to exist in at least two isoforms, one of which (PAP1) is presumed to be cytosolic and membrane associated and the other (PAP2), an integral membrane protein (Brindley and Waggoner, 1996). PAP1 has been implicated in glycerolipid biosynthesis; whereas PAP2 is suggested to play a role in signal transduction. In addition to dephosphorylating PA, purified PAP2 from rat liver has also been found to dephosphorylate lysophosphatidic acid (LPA), ceramide-1-phosphate (C-l-P), sphingosine-1-phosphate (S-l-P) (Waggoner et al., 1996), and DG pyrophosphate (Carman, 1997), suggesting the involvement of PAP2 in modulating the balance of a broad spectrum of bioactive lipids generated during cell signaling. A murine PAP2 cDNA (Kai et al., 1996) and two human cDNAs isoforms, hPAP-2a and hPAP-2b, coding for PAP2 have been identified (Kai et al., 1997). Homology search of the GenBank database using the murine PAP2 sequence probe has also enabled us to isolate several putative human isoenzymes. This paper reports the isolation and expression of two alternatively spliced variants termed PAP2-αl and PAP2-α2 encoded by the human PAP-2a gene and two other isoforms of PAP2 derived from separate genes. |