The diversity and possible functions of the inositol polyphosphate 5-phosphatases

Distinct forms of inositol and phosphatidylinositol polyphosphate 5-phospha tases selectively remove the phosphate from the 5-position of the inositol ring from both soluble and lipid substrates, i.e., inositol 1,4,5-trisphosp hate (Ins(1,4,5)P-3), inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P-4), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P-2) or phosphatidylinos itol 3,4,5-trisphosphate (PtdIns(3,4,5)P-3). In mammalian cells, this famil y contains a series of distinct genes and splice variants. All inositol pol yphosphate 5-phosphatases share a 5-phosphatase domain and various protein modules probably responsible for specific cell localisation or recruitment (SH2 domain, proline-rich sequences, prenylation sites, etc.). Type I Ins(1 ,4,5)P-3 5-phosphatase also uses Ins(1,3,4,5)P-4 but not the phosphoinositi des as substrates. This enzyme is targeted to specific membranes by means o f a prenylation site. Type II 5-phosphatases can use both PtdIns(4,5)P-2 an d PtdIns(3,4,5)P-3 as substrates, Five mammalian enzymes and multiple splic e variants are known: INPP5P or inositol polyphosphate 5-phosphatase II, OC RL (a Golgi protein implicated in the Lowe oculocerebrorenal syndrome), syn aptojanin (a protein involved in the recycling of synaptic vesicles), SHIP 1 and SHIP 2 (or SH2-containing inositol 5-phosphatases). As discussed in t his review, the substrate specificity, regulatory mechanisms, subcellular l ocalisation and tissue specificity indicate that the different 5-phosphatas e isoforms may play specific roles. As known in the dephosphorylation of ty rosine containing substrates by the tyrosine protein phosphatases or in the metabolism of cyclic nucleotides by the cyclic nucleotide phosphodiesteras es, inositol polyphosphate 5-phosphatases directly participate in the contr ol of second messengers in response to both activation or inhibitory cell s ignalling. (C) 1998 Elsevier Science B.V. All rights reserved.