TY - JOUR
T1 - Use of phosphorofluoridate analogues of D-myo-inositol 1,4,5-trisphosphate to assess the involvement of ionic interactions in its recognition by the receptor and metabolising enzymes
AU - Yoshimura, Kenji
AU - Watanabe, Yutaka
AU - Erneux, Christophe
AU - Hirata, Masato
N1 - Funding Information:
This work was funded by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan (to Y. W. and M. H.), the ONO Medical Research Foundation (to M. H.), the Ryoichi Naito Foundation for Medical Research (to M. H.) and the Fukuoka Cancer Society (to M. H.).
PY - 1999/2
Y1 - 1999/2
N2 - D-myo-Inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] analogues fluoridated at 4- or 5-phosphate or both were analysed to assess the involvement of ionic interactions between the phosphates of Ins(1,4,5)P3 and the proteins that recognize it, such as metabolic enzymes and the InsP3 receptor. These analogues were effective in inhibiting type I Ins(1,4,5)P3 5-phosphatase activity with much the same potency as Ins(1,4,5)P3, although the enzyme showed a lower K(m) value as pH values increased. In contrast, the analogues were less potent ligands than Ins(1,4,5)P3 in both the assay of [3H]Ins(1,4,5)P3 binding to the receptors and the phosphorylation of [3H]Ins(1,4,5)P3 catalysed by Ins(1,4,5)P3 3-kinase. These results suggest that ionic interactions with the dianionic 4- and 5-phosphates of Ins(1,4,5)P3 are involved in recognition by the receptor and the kinase, but not by the phosphatase. Copyright (C) 1998 Elsevier Science Inc.
AB - D-myo-Inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] analogues fluoridated at 4- or 5-phosphate or both were analysed to assess the involvement of ionic interactions between the phosphates of Ins(1,4,5)P3 and the proteins that recognize it, such as metabolic enzymes and the InsP3 receptor. These analogues were effective in inhibiting type I Ins(1,4,5)P3 5-phosphatase activity with much the same potency as Ins(1,4,5)P3, although the enzyme showed a lower K(m) value as pH values increased. In contrast, the analogues were less potent ligands than Ins(1,4,5)P3 in both the assay of [3H]Ins(1,4,5)P3 binding to the receptors and the phosphorylation of [3H]Ins(1,4,5)P3 catalysed by Ins(1,4,5)P3 3-kinase. These results suggest that ionic interactions with the dianionic 4- and 5-phosphates of Ins(1,4,5)P3 are involved in recognition by the receptor and the kinase, but not by the phosphatase. Copyright (C) 1998 Elsevier Science Inc.
UR - http://www.scopus.com/inward/record.url?scp=0032923648&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032923648&partnerID=8YFLogxK
U2 - 10.1016/S0898-6568(98)00043-6
DO - 10.1016/S0898-6568(98)00043-6
M3 - Article
C2 - 10048789
AN - SCOPUS:0032923648
SN - 0898-6568
VL - 11
SP - 117
EP - 125
JO - Cellular Signalling
JF - Cellular Signalling
IS - 2
ER -