| Research Abstract |
JNK and p38 subgroups of MAP kinases have been suggested to play a critical role in apoptosis, cell growth and/or differentiation. I found that short cellular stresses, inducing transient activation of JNK and p38, lead to erythroid differentiation rather than apoptosis. Furthermore, activation of JNK and p38 is required for both cell differentiation and apoptosis, and the duration of their activation may determine the cell fate, cell differentiation and apoptosis.
Hematopoietic progenitor kinase-1 (HPK1), which is expressed predominantly in hematopoietic cells, leads to activation of JNK in nonhematopoietic cells. Upstream activators of HPK1 currently remain elusive and its precise role in hematopoiesis has yet to be defined. I therefore examined the possible involvement of HPK1 in erythropoetin (Epo) and environmental stress-induced JNK activation. I found that Epo induces activation of both HPK1 and HS1 while cellular stresses activate only HS1, and that the HPK1-JNK pathway is invol
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ved in Epo-induced growth and differentiation signals.
The regulator of G protein signaling (RGS) negatively regulates the α subunit of G proteins by accelerating their intrinsic GTPase activity. Here I report the isolation and characterization of a novel mouse RGS, termed RGS18. RGS18 mRNA was predominantly detected in spleen and hematopoietic cells, and immunohistochemical studies demonstrated that RGS18 was expressed in megakaryocytes, platelets, granulocytes/monocytes and weakly in hematopoietic stem cells, but not in lymphocytes and erythrocytes. While various subcellular localization of RGS has been reported, RGS18 was found to be localized in cytoplasm in megakaryocytes. In vitro binding assays of RGS18 demonstrated that RGSl8 specifically binds to two α subunits of the G protein, Gαi and Gαq. Furthermore, RGS18 clearly exhibited GAP activity for Gαi and Gαq but not for Gαs or Gα12. In addition, a chemokine SDF-1, which has been reported to stimulate megakaryocyte colony formation in the presence of thrombopoietin, affected the binding of RGS18 to Gαi but not to Gαq. Therefore, the newly isolated RGS18 may play an important role in proliferation, differentiation and/or migration of megakaryocytes. Less
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