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Signaling Pathways That Regulate Normal and Aberrant Red Blood Cell Development

期刊

GENES
卷 12, 期 10, 页码 -

出版社

MDPI
DOI: 10.3390/genes12101646

关键词

kinases; cell signaling; erythropoiesis

资金

  1. NIH T32 training grant [DK098132]
  2. Maternal Child Health Research Institute fellowship [1111239-442-JHACT]
  3. DBA Foundation [138290]
  4. Department of Defense [BM180024]
  5. California Institute of Regenerative Medicine [DISC2-12474]

向作者/读者索取更多资源

Blood cell development is regulated through intrinsic gene regulation and local factors, with signaling pathways involving various kinases. Many cytokines are synthesized and regulated by these pathways, which act both upstream and downstream of the erythropoiesis process. There is still much to be discovered about the nuanced network of kinases responsible for appropriate induction of, and response to, these cytokines.
Blood cell development is regulated through intrinsic gene regulation and local factors including the microenvironment and cytokines. The differentiation of hematopoietic stem and progenitor cells (HSPCs) into mature erythrocytes is dependent on these cytokines binding to and stimulating their cognate receptors and the signaling cascades they initiate. Many of these pathways include kinases that can diversify signals by phosphorylating multiple substrates and amplify signals by phosphorylating multiple copies of each substrate. Indeed, synthesis of many of these cytokines is regulated by a number of signaling pathways including phosphoinositide 3-kinase (PI3K)-, extracellular signal related kinases (ERK)-, and p38 kinase-dependent pathways. Therefore, kinases act both upstream and downstream of the erythropoiesis-regulating cytokines. While many of the cytokines are well characterized, the nuanced members of the network of kinases responsible for appropriate induction of, and response to, these cytokines remains poorly defined. Here, we will examine the kinase signaling cascades required for erythropoiesis and emphasize the importance, complexity, enormous amount remaining to be characterized, and therapeutic potential that will accompany our comprehensive understanding of the erythroid kinome in both healthy and diseased states.

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