| First Author | Kakihana K | Year | 2005 |
| Journal | Biochem Biophys Res Commun | Volume | 335 |
| Issue | 2 | Pages | 424-31 |
| PubMed ID | 16084495 | Mgi Jnum | J:100329 |
| Mgi Id | MGI:3587986 | Doi | 10.1016/j.bbrc.2005.07.095 |
| Citation | Kakihana K, et al. (2005) Calmodulin physically interacts with the erythropoietin receptor and enhances Jak2-mediated signaling. Biochem Biophys Res Commun 335(2):424-31 |
| abstractText | Stimulation of the erythropoietin receptor (EpoR) induces a transient increase in intracellular Ca(2+) level as well as activation of the Jak2 tyrosine kinase to stimulate various downstream signaling pathways. Here, we demonstrate that the universal Ca(2+) receptor calmodulin (CaM) binds EpoR in a Ca(2+)-dependent manner in vitro. Binding studies using various EpoR mutants in hematopoietic cells showed that CaM binds the membrane-proximal 65-amino-acid cytoplasmic region (amino acids 258-312) of EpoR that is critical for activation of Jak2-mediated EpoR signaling. Structurally unrelated CaM antagonists, W-13 and CMZ, inhibited activation of Jak2-mediated EpoR signaling pathways, whereas W-12, a W-13 analog, did not show any significant inhibitory effect. Moreover, overexpression of CaM augmented Epo-induced tyrosine phosphorylation of the EpoR. W-13, but not W-12, also inhibited Epo-induced proliferation and survival. Together, these results indicate that CaM binds to the membrane-proximal EpoR cytoplasmic region and plays an essential role in activation of Jak2-mediated EpoR signaling. |
