Biology:PIK3CG

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform is an enzyme that in humans is encoded by the PIK3CG gene.

Function

This gene encodes a protein that belongs to the pi3/pi4-kinase family of proteins. The gene product is an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring. It is an important modulator of extracellular signals, including those elicited by E-cadherin-mediated cell-cell adhesion, which plays an important role in maintenance of the structural and functional integrity of epithelia. In addition to its role in promoting assembly of adherens junctions, the protein is thought to play a pivotal role in the regulation of cytotoxicity in NK cells. The gene is located in a commonly deleted segment of chromosome 7 previously identified in myeloid leukemias.[1] More recently, this gene has been shown to be a critical myeloid-restricted vulnerability in Acute Myeloid Leukemia (AML). Its targeting, either by the small-molecule inhibitor IPI-549 or by a first-in-class proteolysis-targeting chimera (PROTAC) named ARM165, has been shown to reduce AML cell progression both in vitro and in vivo.[2][3]

Interactions

PIK3CG has been shown to interact with:

See also

References

  1. ↑ "Entrez Gene: PIK3CG phosphoinositide-3-kinase, catalytic, gamma polypeptide". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=5294. 
  2. ↑ "Targetable leukaemia dependency on noncanonical PI3Kγ signalling". Nature 630 (8015): 198–205. 2024. doi:10.1038/s41586-024-07410-3. PMID 38720074. Bibcode: 2024Natur.630..198L. 
  3. ↑ "Targeting a lineage-specific PI3Kɣ-Akt signaling module in acute myeloid leukemia using a heterobifunctional degrader molecule". Nature Cancer 5 (7): 1082–1101. 2024. doi:10.1038/s43018-024-00782-5. PMID 38816660. 
  4. ↑ "The SH2-containing adapter protein GRB10 interacts with BCR-ABL". Oncogene 17 (8): 941–8. August 1998. doi:10.1038/sj.onc.1202024. PMID 9747873. 
  5. ↑ "p210BCR/ABL induces formation of complexes containing focal adhesion proteins and the protooncogene product p120c-Cbl". Exp. Hematol. 24 (2): 310–3. February 1996. PMID 8641358. 
  6. ↑ "Phosphatidylinositol-3 kinase activity is regulated by BCR/ABL and is required for the growth of Philadelphia chromosome-positive cells". Blood 86 (2): 726–36. July 1995. doi:10.1182/blood.V86.2.726.bloodjournal862726. PMID 7606002. 
  7. ↑ "Farnesylation of Ras is important for the interaction with phosphoinositide 3-kinase gamma". Eur. J. Biochem. 266 (1): 70–82. November 1999. doi:10.1046/j.1432-1327.1999.00815.x. PMID 10542052. 
  8. ↑ "P110delta, a novel phosphoinositide 3-kinase in leukocytes". Proc. Natl. Acad. Sci. U.S.A. 94 (9): 4330–5. April 1997. doi:10.1073/pnas.94.9.4330. PMID 9113989. Bibcode: 1997PNAS...94.4330V. 
  9. ↑ "Roles of G beta gamma in membrane recruitment and activation of p110 gamma/p101 phosphoinositide 3-kinase gamma". J. Cell Biol. 160 (1): 89–99. January 2003. doi:10.1083/jcb.200210115. PMID 12507995. 

Further reading

  • "Phosphoinositide 3-kinase gamma: kinase-dependent and -independent activities in cardiovascular function and disease.". Biochem. Soc. Trans. 32 (Pt 2): 383–6. 2004. doi:10.1042/BST0320383. PMID 15046613. 
  • "PI3K delta and PI3K gamma: partners in crime in inflammation in rheumatoid arthritis and beyond?". Nat. Rev. Immunol. 7 (3): 191–201. 2007. doi:10.1038/nri2036. PMID 17290298. 




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