1y19

Structural highlights

Function

PI51C_MOUSE Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). PtdIns(4,5)P2 is involved in a variety of cellular processes and is the substrate to form phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), another second messenger. The majority of PtdIns(4,5)P2 is thought to occur via type I phosphatidylinositol 4-phosphate 5-kinases given the abundance of PtdIns4P. Participates in a variety of cellular processes such as vesicle mediated transport, cell adhesion, cell polarization and cell migration. Together with PIP5K1A is required for phagocytosis, but they regulate different types of actin remodeling at sequential steps. Promotes particle attachment by generating the pool of PtdIns(4,5)P2 that induces controlled actin depolymerization to facilitate Fc-gamma-R clustering. Mediates RAC1-dependent reorganization of actin filaments. Required for synaptic vesicle transport. Controls the plasma membrane pool of PtdIns(4,5)P2 implicated in synaptic vesicle endocytosis and exocytosis. Plays a role in endocytosis mediated by clathrin and AP-2 (adaptor protein complex 2). Required for clathrin-coated pits assembly at the synapse. Participates in cell junction assembly. Modulates adherens junctions formation by facilitating CDH1 trafficking. Required for focal adhesion dynamics. Modulates the targeting of talins (TLN1 and TLN2) to the plasma membrane and their efficient assembly into focal adhesions. Regulates the interaction between talins (TLN1 and TLN2) and beta-integrins. Required for uropodium formation and retraction of the cell rear during directed migration. Has a role in growth factor- stimulated directional cell migration and adhesion. Required for talin assembly into nascent adhesions forming at the leading edge toward the direction of the growth factor. Negative regulator of T-cell activation and adhesion. Negatively regulates integrin alpha-L/beta-2 (LFA-1) polarization and adhesion induced by T-cell receptor. Together with PIP5K1A have a role during embryogenesis and together with PIP5K1B may have a role immediately after birth.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Talin 3D structures

References

1. ↑ Ishihara H, Shibasaki Y, Kizuki N, Wada T, Yazaki Y, Asano T, Oka Y. Type I phosphatidylinositol-4-phosphate 5-kinases. Cloning of the third isoform and deletion/substitution analysis of members of this novel lipid kinase family. J Biol Chem. 1998 Apr 10;273(15):8741-8. PMID:9535851
2. ↑ Ling K, Doughman RL, Firestone AJ, Bunce MW, Anderson RA. Type I gamma phosphatidylinositol phosphate kinase targets and regulates focal adhesions. Nature. 2002 Nov 7;420(6911):89-93. PMID:12422220 doi:http://dx.doi.org/10.1038/nature01082
3. ↑ Di Paolo G, Moskowitz HS, Gipson K, Wenk MR, Voronov S, Obayashi M, Flavell R, Fitzsimonds RM, Ryan TA, De Camilli P. Impaired PtdIns(4,5)P2 synthesis in nerve terminals produces defects in synaptic vesicle trafficking. Nature. 2004 Sep 23;431(7007):415-22. PMID:15386003 doi:http://dx.doi.org/10.1038/nature02896
4. ↑ Bairstow SF, Ling K, Su X, Firestone AJ, Carbonara C, Anderson RA. Type Igamma661 phosphatidylinositol phosphate kinase directly interacts with AP2 and regulates endocytosis. J Biol Chem. 2006 Jul 21;281(29):20632-42. Epub 2006 May 17. PMID:16707488 doi:http://dx.doi.org/10.1074/jbc.M601465200
5. ↑ Sun Y, Ling K, Wagoner MP, Anderson RA. Type I gamma phosphatidylinositol phosphate kinase is required for EGF-stimulated directional cell migration. J Cell Biol. 2007 Jul 16;178(2):297-308. PMID:17635937 doi:10.1083/jcb.200701078
6. ↑ Lokuta MA, Senetar MA, Bennin DA, Nuzzi PA, Chan KT, Ott VL, Huttenlocher A. Type Igamma PIP kinase is a novel uropod component that regulates rear retraction during neutrophil chemotaxis. Mol Biol Cell. 2007 Dec;18(12):5069-80. Epub 2007 Oct 10. PMID:17928408 doi:http://dx.doi.org/10.1091/mbc.E07-05-0428
7. ↑ Wang Y, Lian L, Golden JA, Morrisey EE, Abrams CS. PIP5KI gamma is required for cardiovascular and neuronal development. Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11748-53. Epub 2007 Jul 3. PMID:17609388 doi:http://dx.doi.org/10.1073/pnas.0700019104
8. ↑ Mao YS, Yamaga M, Zhu X, Wei Y, Sun HQ, Wang J, Yun M, Wang Y, Di Paolo G, Bennett M, Mellman I, Abrams CS, De Camilli P, Lu CY, Yin HL. Essential and unique roles of PIP5K-gamma and -alpha in Fcgamma receptor-mediated phagocytosis. J Cell Biol. 2009 Jan 26;184(2):281-96. doi: 10.1083/jcb.200806121. Epub 2009 Jan, 19. PMID:19153220 doi:http://dx.doi.org/10.1083/jcb.200806121
9. ↑ Volpicelli-Daley LA, Lucast L, Gong LW, Liu L, Sasaki J, Sasaki T, Abrams CS, Kanaho Y, De Camilli P. Phosphatidylinositol-4-phosphate 5-kinases and phosphatidylinositol 4,5-bisphosphate synthesis in the brain. J Biol Chem. 2010 Sep 10;285(37):28708-14. doi: 10.1074/jbc.M110.132191. Epub, 2010 Jul 9. PMID:20622009 doi:http://dx.doi.org/10.1074/jbc.M110.132191
10. ↑ Wernimont SA, Legate KR, Simonson WT, Fassler R, Huttenlocher A. PIPKI gamma 90 negatively regulates LFA-1-mediated adhesion and activation in antigen-induced CD4+ T cells. J Immunol. 2010 Oct 15;185(8):4714-23. doi: 10.4049/jimmunol.1001445. Epub 2010, Sep 20. PMID:20855869 doi:http://dx.doi.org/10.4049/jimmunol.1001445
11. ↑ de Pereda JM, Wegener KL, Santelli E, Bate N, Ginsberg MH, Critchley DR, Campbell ID, Liddington RC. Structural basis for phosphatidylinositol phosphate kinase type Igamma binding to talin at focal adhesions. J Biol Chem. 2005 Mar 4;280(9):8381-6. Epub 2004 Dec 28. PMID:15623515 doi:10.1074/jbc.M413180200