Signaling Pathways That Regulate Normal and Aberrant Red Blood Cell Development

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:12

Enthalten in:

Genes - 12(2021), 10 vom: 19. Okt.

Sprache:

Englisch

Beteiligte Personen:

Wilkes, Mark C [VerfasserIn]
Shibuya, Aya [VerfasserIn]
Sakamoto, Kathleen M [VerfasserIn]

Links:

Volltext

Themen:

Cell signaling
EC 2.7.11.24
Erythropoiesis
Extracellular Signal-Regulated MAP Kinases
Journal Article
Kinases
Research Support, N.I.H., Extramural
Review

Anmerkungen:

Date Completed 08.02.2022

Date Revised 16.07.2022

published: Electronic

Citation Status MEDLINE

doi:

10.3390/genes12101646

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM332211827