Function, Regulation and Biological Roles of PI3Kγ Variants
Abstract
:1. Introduction
2. Identification of PI3Kγ and Its Tissue Distribution
2.1. PI3Kγ—Catalytic and Regulatory Subunits
2.2. Tissue Distribution of PI3Kγ
3. Regulation of PI3Kγ by Gβγ
3.1. Regulation of PI3Kγ by Heterotrimeric G-Proteins
3.1.1. Identification of Gβγ-Binding Sites on PI3Kγ
3.1.2. Regulation of PI3Kγ Activity by Gβγ
3.1.3. Differential Regulation of p101–p110γ and p87–p110γ by Gβγ
3.1.4. Gβγ-Isoform Specificity for PI3Kγ Activation
3.2. Activation of PI3Kγ by Small GTPases
4. Protein Kinase Activity of PI3Kγ
5. Non-Catalytic Functions of PI3Kγ
6. Biological Functions of PI3Kγ
6.1. Immune System
6.2. Platelets
6.3. Cardiovascular System
6.4. Metabolism
6.5. Nervous System
6.6. Cancer
7. Pharmacological Inhibitors of PI3Kγ
Funding
Acknowledgments
Conflicts of Interest
References
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Organ/Tissue/Cell Type | p87 | p101 |
---|---|---|
Immune System | ||
Bone Marrow | +++ | +++ |
Lymph Node | +++ | +++ |
Plasma Blood Leukocytes | +++ | +++ |
Spleen | +++ | +++ |
Thymus | ++ | +++ |
Tonsil | ++ | + |
Cardiovascular System | ||
Heart | + | n.d. |
Intracranial Artery | + | n.d. |
Vena Cava | + | n.d. |
Metabolic Organs | ||
Colon | + | + |
Duodenum (descending part) | + | + |
Esophagus | + | n.d. |
Fat | ++ | + |
Intestine (small) | ++ | + |
Liver | n.d. | + |
Pancreas | + | n.d. |
Rectum | +++ | n.d. |
Stomach | ++ | ++ |
Nervous System | ||
Brain | + | + |
Optic Nerve | + | n.d. |
Pituitary Gland | + | + |
Retina | + | + |
Spinal Cord | + | + |
Others | ||
Lung | ++ | +++ |
Mammary Gland | + | n.d. |
Ovary | + | n.d. |
Prostate | ++ | + |
Skin | ++ | + |
Urethra | ++ | n.d. |
p87−/− | p101−/− | |
---|---|---|
Thymocytes | not impaired | requirement for β-selection during thymocyte development |
Neutrophils | impaired PIP3 production and Akt phosphorylation, as well as less ROS formation, but normal migration | impaired PIP3 production, as well as Akt phosphorylation and migration, but normal ROS formation |
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Nürnberg, B.; Beer-Hammer, S. Function, Regulation and Biological Roles of PI3Kγ Variants. Biomolecules 2019, 9, 427. https://doi.org/10.3390/biom9090427
Nürnberg B, Beer-Hammer S. Function, Regulation and Biological Roles of PI3Kγ Variants. Biomolecules. 2019; 9(9):427. https://doi.org/10.3390/biom9090427
Chicago/Turabian StyleNürnberg, Bernd, and Sandra Beer-Hammer. 2019. "Function, Regulation and Biological Roles of PI3Kγ Variants" Biomolecules 9, no. 9: 427. https://doi.org/10.3390/biom9090427