Inositol polyphosphate 4-phosphatase type I regulates cell growth downstream of transcription factor GATA-1.
Megakaryocytes lacking transcription factor GATA-1 fail to complete maturation in vivo and hyperproliferate. To define how GATA-1 regulates megakaryocyte cell growth we searched for mRNA transcripts expressed in primary wild-type, but not GATA-1(-), megakaryocytes. One differentially expressed transcript encodes inositol polyphosphate 4-phosphatase type I (4-Ptase I). This enzyme hydrolyses phosphatidylinositol 3,4-bisphosphate and also has lesser activity against soluble analogues of this lipid, inositol 3, 4-bisphosphate and inositol 1,3,4-triphosphate. Reintroduction of 4-Ptase I into both primary GATA-1(-) and wild-type megakaryocytes significantly retards cell growth, suggesting that absence of 4-Ptase I may contribute to the hyperproliferative phenotype of GATA-1(-) megakaryocytes. Overexpression of 4-Ptase I also markedly reduces growth of NIH 3T3 fibroblasts. Taken together, these data indicate that 4-Ptase I is a regulator of cell proliferation.
Vyas
P
P
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9AE, United Kingdom.
Norris
F A
FA
Joseph
R
R
Majerus
P W
PW
Orkin
S H
SH
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000502:physiology*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D050981:Erythroid-Specific DNA-Binding Factors; D005347:Fibroblasts / Q000166:cytology; D050982:GATA1 Transcription Factor; D008533:Megakaryocytes / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D014157:Transcription Factors; D010744:Phosphoric Monoester Hydrolases; C053153:phosphatidylinositol-3,4-bisphosphate 4-phosphatase