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Blood, 1 May 2006, Vol. 107, No. 9, pp. 3527-3530.
Prepublished online as a Blood First Edition Paper on January 3, 2006; DOI 10.1182/blood-2005-10-4309.


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Submitted November 3, 2005
Accepted December 16, 2005

Phosphorylation of Gata1 at serine residues 72, 142 and 310 is not essential for hematopoiesis in vivo

Heather M Rooke and Stuart H Orkin*

Division of Hematology/Oncology, Children's Hospital Boston and the Dana Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Howard Hughes Medical Institute, Boston, MA, USA
Division of Hematology/Oncology, Children's Hospital Boston and the Dana Farber Cancer Institute, Boston, MA, USA; Howard Hughes Medical Institute, Boston, MA, USA

* Corresponding author; email: orkin{at}bloodgroup.tch.harvard.edu.

Phosphorylation of transcription factors is important in post-translational control of protein function. The indispensable zinc-finger transcription factor, Gata1, is phosphorylated constitutively at six serine residues (26, 49, 72, 142, 178, 187) and at a seventh (310) following induction of erythroid differentiation. However, the biological consequences of phosphorylation with respect to function are unclear. To address this issue, we generated mice with serine to alanine mutations at the inducibly-phosphorylated serine 310 alone or at conserved serine residues 72, 142 and 310 together. The peripheral blood parameters of the mice were normal, as was their response to acute erythropoietic stress. Analysis of hematopoietic progenitor populations during ontogeny and into adulthood showed a moderate decrease in BFU-E and CFU-E numbers only in the adult bone marrow of the triple mutant. Yet, later stage erythropoiesis was not perturbed. This suggests that any molecular consequences associated with loss of phosphorylation at residues 72, 142 and 310 can be compensated for in the in vivo environment.


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