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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.

Original publication

DOI

10.1073/pnas.250476397

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

05/12/2000

Volume

97

Pages

13696 - 13701

Keywords

3T3 Cells, Animals, Base Sequence, Cell Division, DNA Primers, DNA-Binding Proteins, Erythroid-Specific DNA-Binding Factors, Fibroblasts, GATA1 Transcription Factor, Megakaryocytes, Mice, Mice, Knockout, Molecular Sequence Data, Phosphoric Monoester Hydrolases, Transcription Factors