Abstract
Macrophages display an array of activation phenotypes depending on the activation signal and the cellular microenvironment. The type and magnitude of the response depend on signaling molecules as well as on the epigenetic and metabolic status of the cells at the time of activation. The AKT family of kinases consists of three isoforms encoded by independent genes possessing similar functions and structures. Generation of research tools such as isoform-specific gene deletion mutant mice and cells and isoform-specific antibodies has allowed us to understand the role of each kinase isoform in macrophage activation and homeostasis. This chapter discusses the current evidence on the role of AKT kinases in macrophage activation, polarization, and homeostasis, highlighting the gaps in knowledge and future challenges in the field.
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Abbreviations
- α-KG:
-
α-Ketoglutarate
- ACLY:
-
ATP citrate lyase
- AMPK:
-
AMP-activated protein kinase
- CLRs:
-
C-type lectin receptors
- FAD:
-
Flavin adenine dinucleotide
- HAT:
-
Histone acetyltransferases
- HK:
-
Hexokinase
- IRF:
-
Interferon regulatory factor
- JAK:
-
Janus kinase
- jmjC:
-
Jumonji-C
- LTA:
-
Lipoteichoic acid
- MerTK:
-
Mer receptor tyrosine kinase
- miRs:
-
Micro RNAs
- MAPK:
-
Mitogen-activated protein kinase
- mTOR:
-
Mammalian Target of Rapamycin
- MyD88:
-
Myeloid differentiation primary response gene 88
- NAD:
-
Nicotinamide adenine dinucleotide
- NADPH:
-
Nicotinamide adenine dinucleotide phosphate
- NLRs:
-
Nucleotide-binding leucine-rich repeat-containing receptors
- ODN:
-
Oligodeoxynucleotide
- oxLDL:
-
Oxidized Low Density Lipoprotein
- PFKP1/2:
-
Phosphofructokinase1/2
- PH:
-
Pleckstrin homology
- RLRs:
-
RIG-I-like receptors
- ROS:
-
Reactive oxygen species
- SAM:
-
S-adenosylmethionine
- SHIP1:
-
SH2 domain-containing inositol-5-phosphatase 1
- SOCS:
-
Suppressor of cytokine signaling
- TAMs:
-
Tumor-associated macrophages
- TBK1:
-
TANK-binding kinase 1
- TGF-β:
-
Transforming growth factor-beta
- TLRs:
-
Toll-like receptors
- TRIF:
-
TIR domain-containing adaptor-inducing interferons
- VIP:
-
Vasoactive intestinal peptide
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Acknowledgments
In memoriam of Dr Alicia Arranz, who pioneered work in the field. Funding information: This work was supported by the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship, and Innovation, under the call RESEARCH—CREATE—INNOVATE, T1EDK-04048 and by the Hellenic Foundation for Research and Innovation grant HFRI, General Secretariat for Research and Technology, GSRT Grant No 1010.
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Lapi, I. et al. (2022). AKT Isoforms in Macrophage Activation, Polarization, and Survival. In: Dominguez-Villar, M. (eds) PI3K and AKT Isoforms in Immunity . Current Topics in Microbiology and Immunology, vol 436. Springer, Cham. https://doi.org/10.1007/978-3-031-06566-8_7
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