Regulation of Hematopoietic Cell Development and Function Through Phosphoinositides

Frontiers in Immunology
Mila Elich, Karsten Sauer

Abstract

One of the most paramount receptor-induced signal transduction mechanisms in hematopoietic cells is production of the lipid second messenger phosphatidylinositol(3,4,5)trisphosphate (PIP3) by class I phosphoinositide 3 kinases (PI3K). Defective PIP3 signaling impairs almost every aspect of hematopoiesis, including T cell development and function. Limiting PIP3 signaling is particularly important, because excessive PIP3 function in lymphocytes can transform them and cause blood cancers. Here, we review the key functions of PIP3 and related phosphoinositides in hematopoietic cells, with a special focus on those mechanisms dampening PIP3 production, turnover, or function. Recent studies have shown that beyond "canonical" turnover by the PIP3 phosphatases and tumor suppressors phosphatase and tensin homolog (PTEN) and SH2 domain-containing inositol-5-phosphatase-1 (SHIP-1/2), PIP3 function in hematopoietic cells can also be dampened through antagonism with the soluble PIP3 analogs inositol(1,3,4,5)tetrakisphosphate (IP4) and inositol-heptakisphosphate (IP7). Other evidence suggests that IP4 can promote PIP3 function in thymocytes. Moreover, IP4 or the kinases producing it limit store-operated Ca2+ entry through Orai channels in B c...Continue Reading

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Citations

Jul 10, 2020·International Journal of Molecular Sciences·Hee Jun ChoHaiyoung Jung
Jan 8, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Haiying TangZhou Zhu
Nov 26, 2020·Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology·Riccardo Castagnoli, Luigi Daniele Notarangelo
Feb 2, 2021·Small GTPases·Laila Karra, Jeroen P Roose
Mar 23, 2021·Human Immunology·Nathalie Rouas-FreissEdgardo D Carosella

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Methods Mentioned

BETA
nucleotide exchange
transgenic
exome sequencing

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