Type I Cytokine Receptors - Erythropoietin Receptor (Paperback)

Purchase includes free access to book updates online and a free trial membership in the publisher's book club where you can select from more than a million books without charge. Excerpt: The erythropoietin receptor (EpoR) is a 66 kDa peptide consisting of two peptide chains and is a member of the cytokine receptor family. Upon binding of a 34 kDa ligand erythropoietin (Epo), the two chains of the EpoR undergo a conformational change resulting in the autophosphorylation of Jak2 kinases that are pre-associated with the receptor (i.e., EpoR does not possess intrinsic kinase activity and depends on Jak2 activity). The cytoplasmic domains of the EpoR contain a number of phosphotyrosines that are phosphorylated by Jak2 and serve as docking sites for a variety of intracellular pathway activators and Stats (such as Stat5). In addition to activating Ras/MAP kinase, phosphatidylinositol 3-kinase/AKT pathway and STAT transcription factors, phosphotyrosines also serve as docking sites for phosphatases that negatively affect EpoR signaling in order to prevent overactivation that may lead to such disorders as erythrocytosis. In general, the defects in the erythropoietin receptor may produce erythroleukemia and familial erythrocytosis. It is interesting to note that mice with truncated EpoR are viable, supporting the idea that Jak2 activity is sufficient to support basal erythropoiesis by activating the necessary pathways without phosphotyrosine docking sites being needed. EpoR-H form of EpoR truncation contains the first, and, what can be argued, the most important tyrosine 343 that serves as a docking site for the Stat5 molecule, but lacks the rest of the cytoplasmic tail. These mice exhibit elevated erythropoiesis consistent with the idea that phosphatase recruitment (and therefore the shutting down of signaling) is aberrant in these mice. The EpoR-HM receptor lacks the cytoplasmic domain with the tyrosine 343 mutated to phenylalanine, ... More: http://booksllc.net/?id=5827434