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PMID:20940048

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Citation

Fung-Leung, WP (2011) Phosphoinositide 3-kinase delta (PI3Kδ) in leukocyte signaling and function. Cell. Signal. 23:603-8

Abstract

PI3Kδ is a lipid kinase of the PI3K class IA family involved in early signaling events of leukocytes responding to a wide variety of stimuli. The leukocyte specificity of PI3Kδ is defined by its expression, whereas its signaling function is via the production of phosphoinositide 3,4,5-triphosphates at the proximity of activated receptors for recruiting other signaling molecules. The importance of PI3Kδ in B cell development and function is most apparent, and its role in other leukocyte cell types can be easily demonstrated as well. PI3Kδ participates in the development, activation and migration of T cells and NK cells. The role of PI3Kδ in myeloid cell activities, such as inflammation driven cell infiltration, neutrophil oxidative burst, immune complex mediated macrophage activation, as well as mast cell maturation and degranulation, has been well illustrated in various studies. As a result of the broad effects of PI3Kδ in leukocyte functions, the disruption of PI3Kδ expression or activity leads to decreased inflammatory and immune responses in vivo. The protective role of PI3Kδ inactivation in animal models of arthritis, asthma or obstructive respiratory diseases has been demonstrated. These findings suggest the potential efficacy achievable with PI3Kδ inhibitors in the treatment of autoimmune and respiratory diseases.

Links

PubMed Online version:10.1016/j.cellsig.2010.10.002

Keywords

Animals; Asthma/enzymology; Autoimmune Diseases/enzymology; B-Lymphocytes/enzymology; B-Lymphocytes/physiology; Humans; Hypersensitivity/enzymology; Immunity, Cellular; Killer Cells, Natural/enzymology; Killer Cells, Natural/physiology; Leukocytes/enzymology; Leukocytes/physiology; Myeloid Cells/enzymology; Myeloid Cells/physiology; Phosphatidylinositol 3-Kinase/metabolism; Pulmonary Disease, Chronic Obstructive/enzymology; Signal Transduction; T-Lymphocytes/enzymology; T-Lymphocytes/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:PK3CD

involved_in

GO:0001819: positive regulation of cytokine production

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PK3CD

involved_in

GO:0006954: inflammatory response

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PK3CD

involved_in

GO:0045087: innate immune response

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PK3CD

involved_in

GO:0010818: T cell chemotaxis

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PK3CD

involved_in

GO:0030217: T cell differentiation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PK3CD

involved_in

GO:0030101: natural killer cell activation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PK3CD

involved_in

GO:0030593: neutrophil chemotaxis

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PK3CD

involved_in

GO:0035754: B cell chemotaxis

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PK3CD

involved_in

GO:0035747: natural killer cell chemotaxis

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PK3CD

involved_in

GO:0042110: T cell activation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PK3CD

involved_in

GO:0042113: B cell activation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PK3CD

involved_in

GO:0043303: mast cell degranulation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PK3CD

involved_in

GO:0050852: T cell receptor signaling pathway

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PK3CD

involved_in

GO:0050853: B cell receptor signaling pathway

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PK3CD

involved_in

GO:0060374: mast cell differentiation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PK3CD

involved_in

GO:0072672: neutrophil extravasation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PK3CD

involved_in

GO:0002679: respiratory burst involved in defense response

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PK3CD

involved_in

GO:0002551: mast cell chemotaxis

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PK3CD

involved_in

GO:0001816: cytokine production

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PK3CD

involved_in

GO:0001779: natural killer cell differentiation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

See also

References

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