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Integrating novel signaling pathways involved in erythropoiesis
Author(s) -
Ingley Evan
Publication year - 2012
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.1024
Subject(s) - lyn , erythropoiesis , microbiology and biotechnology , signal transduction , erythropoietin , biology , mapk/erk pathway , erythropoietin receptor , protein kinase b , kinase , cell signaling , proto oncogene tyrosine protein kinase src , medicine , endocrinology , anemia
Abstract Many extrinsic and intrinsic factors control the development of red blood cells from committed progenitors, with the Erythropoietin‐receptor (Epo‐R) signaling network being the primary controlling molecular hub. Although much is understood about erythroid signaling pathways, new and intriguing factors that influence different aspects of erythroid cell development are still being uncovered. New extrinsic effectors include hypoxia and polymeric IgA1 (pIgA1), and new Epo‐R signaling pathway components include Lyn/Cbp and Lyn/Liar. Hypoxia directly activates committed erythroid progenitors to expand, whereas pIgA1 activates the Akt and MAP‐Kinase (MAPK) pathways through transferrin receptors on more mature erythroid cells. The Lyn/Cbp pathway controls the activity and protein levels of Lyn through recruitment of Csk and SOCS1, as well as feeding into the control of other pathways mediated by recruitment of ras‐GAP, PI3‐kinase, PLCγ, Fes, and EBP50. Nuclear/cytoplasmic shuttling of Lyn and other signaling molecules is influenced by Liar and results in regulation of their intersecting signaling pathways. The challenge of future research is to flesh out the details of these new signaling regulators/networks and integrate their influences during the different stages of erythropoiesis. 2012 IUBMB IUBMB Life, 2012