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Kinase AKT controls innate immune cell development and function - PubMed

Review

Kinase AKT controls innate immune cell development and function

Yan Zhang et al. Immunology. 2013 Oct.

Abstract

The critical roles of kinase AKT in tumour cell proliferation, apoptosis and protein synthesis have been widely recognized. But AKT also plays an important role in immune modulation. Recent studies have confirmed that kinase AKT can regulate the development and functions of innate immune cells (neutrophil, macrophage and dendritic cell). Studies have shown that different isoforms of kinase AKT have different effects in regulating immunity-related diseases, mainly through the mammalian target of rapamycin-dependent or -independent pathways. The purpose of this review is to illustrate the immune modulating effects of kinase AKT on innate immune cell development, survival and function.

Keywords: homeostasis; immunity; innate immunity; kinase AKT; modulation; molecular mechanisms.

© 2013 John Wiley & Sons Ltd.

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Figures

Figure 1
Figure 1

AKT-mammalian target of rapapmycin (mTOR) signalling pathway. The mTOR forms two structurally and functionally distinct complexes mTORC1 and mTORC2. Activity of mTORC1 is critically controlled by a small GTPase, Rheb, whose activity is inhibited by a GTPase-activating protein, tuberous sclerosis protein 2 (TSC2) in complex with TSC1. Many accessory molecules as well as growth factors signal via the PI3K–AKT. AKT can further promote mTORC1 activity independent of TSC1/2 by phosphorylating PRAS40, a negative regulator of mTORC1 activity. Further mTORC1 can be activated via the WNT pathway, in a signalling cascade involving glycogen synthase kinase 3 (GSK3).

Figure 2
Figure 2

AKT controls T-cell differentiation. AKT–mammalian target of rapamycin (mTOR) control CD4+ T-cell differentiation. The complexes mTORC1 and mTORC2 have different physiological functions. mTORC1 signalling promotes T helper type 1 (Th1) and Th17 differentiation; mTORC2 promotes Th2 differentiation; and inhibition of mTOR leads to regulatory T (Treg) cells through the transforming growth factor-β (TGF-β)-Smad3 pathway.

Figure 3
Figure 3

AKT control innate immune cell homeostasis and activity. Dendritic cells, macrophages and neutrophils could be activated by all kinds of stimuli, lipopolysaccharide (LPS) or fMet-Leu-Phe (fMLP). The activated AKT control immune cell cytokine secretion, reactive oxygen species production, and maintain cell homeostasis by regulating the balance between apoptosis and proliferation by glycogen synthase kinase.

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