Inositol polyphosphate 4-phosphatase type I regulates cell growth downstream of transcription factor GATA-1
Copyright policy )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.
- University of Oxford United Kingdom
- Harvard University United States
- University of Mary United States
- Iowa State University United States
- Northamptonshire Healthcare NHS Foundation Trust United Kingdom
Mice, Knockout, Base Sequence, Molecular Sequence Data, 3T3 Cells, Fibroblasts, Phosphoric Monoester Hydrolases, DNA-Binding Proteins, Mice, Animals, Erythroid-Specific DNA-Binding Factors, GATA1 Transcription Factor, Megakaryocytes, Cell Division, DNA Primers, Transcription Factors
Mice, Knockout, Base Sequence, Molecular Sequence Data, 3T3 Cells, Fibroblasts, Phosphoric Monoester Hydrolases, DNA-Binding Proteins, Mice, Animals, Erythroid-Specific DNA-Binding Factors, GATA1 Transcription Factor, Megakaryocytes, Cell Division, DNA Primers, Transcription Factors
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