The Inositol Polyphosphate 4-phosphatase Forms a Complex with Phosphatidylinositol 3-kinase in Human Platelet Cytosol

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1999 Mar 31

PMID 10097090

Citations 12

Authors

A D Munday

F A Norris

K K Caldwell

S Brown

P W MAJERUS

C A Mitchell

Affiliations

Soon will be listed here.

Abstract

Inositol polyphosphate 4-phosphatase (4-phosphatase) is an enzyme that catalyses the hydrolysis of the 4-position phosphate from phosphatidylinositol 3,4-bisphosphate [PtdIns(3,4)P2]. In human platelets the formation of this phosphatidylinositol, by the actions of phosphatidylinositol 3-kinase (PI 3-kinase), correlates with irreversible platelet aggregation. We have shown previously that a phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase forms a complex with the p85 subunit of PI 3-kinase. In this study we investigated whether PI 3-kinase also forms a complex with the 4-phosphatase in human platelets. Immunoprecipitates of the p85 subunit of PI 3-kinase from human platelet cytosol contained 4-phosphatase enzyme activity and a 104-kDa polypeptide recognized by specific 4-phosphatase antibodies. Similarly, immunoprecipitates made using 4-phosphatase-specific antibodies contained PI 3-kinase enzyme activity and an 85-kDa polypeptide recognized by antibodies to the p85 adapter subunit of PI 3-kinase. After thrombin activation, the 4-phosphatase translocated to the actin cytoskeleton along with PI 3-kinase in an integrin- and aggregation-dependent manner. The majority of the PI 3-kinase/4-phosphatase complex (75%) remained in the cytosolic fraction. We propose that the complex formed between the two enzymes serves to localize the 4-phosphatase to sites of PtdIns(3,4)P2 production.

Citing Articles

Plausible role of INPP4A dysregulation in idiopathic pulmonary fibrosis.

Arvind M, Pattnaik B, Gheware A, Prakash Y, Srivastava M, Agrawal A Physiol Rep. 2024; 12(9):e16032.

PMID: 38720166 PMC: 11078778. DOI: 10.14814/phy2.16032.

Signaling Enzymes and Ion Channels Being Modulated by the Actin Cytoskeleton at the Plasma Membrane.

Vasilev F, Ezhova Y, Chun J Int J Mol Sci. 2021; 22(19).

PMID: 34638705 PMC: 8508623. DOI: 10.3390/ijms221910366.

Class I PI3K Provide Lipid Substrate in T Cell Autophagy Through Linked Activity of Inositol Phosphatases.

McLeod I, Saxena R, Carico Z, He Y Front Cell Dev Biol. 2021; 9:709398.

PMID: 34458267 PMC: 8397451. DOI: 10.3389/fcell.2021.709398.

Secretory Inositol Polyphosphate 4-Phosphatase Protects against Airway Inflammation and Remodeling.

Khanna K, Chaudhuri R, Aich J, Pattnaik B, Panda L, Prakash Y Am J Respir Cell Mol Biol. 2018; 60(4):399-412.

PMID: 30335467 PMC: 6444634. DOI: 10.1165/rcmb.2017-0353OC.

Class III PI 3-kinase is the main source of PtdIns3P substrate and membrane recruitment signal for PIKfyve constitutive function in podocyte endomembrane homeostasis.

Ikonomov O, Sbrissa D, Venkatareddy M, Tisdale E, Garg P, Shisheva A Biochim Biophys Acta. 2015; 1853(5):1240-50.

PMID: 25619930 PMC: 4431544. DOI: 10.1016/j.bbamcr.2015.01.008.

References

Banfic H, Downes C, Rittenhouse S . Biphasic activation of PKBalpha/Akt in platelets. Evidence for stimulation both by phosphatidylinositol 3,4-bisphosphate, produced via a novel pathway, and by phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem. 1998; 273(19):11630-7. DOI: 10.1074/jbc.273.19.11630. View

Downward J . Mechanisms and consequences of activation of protein kinase B/Akt. Curr Opin Cell Biol. 1998; 10(2):262-7. DOI: 10.1016/s0955-0674(98)80149-x. View

Zhang J, Banfic H, Straforini F, Tosi L, Volinia S, Rittenhouse S . A type II phosphoinositide 3-kinase is stimulated via activated integrin in platelets. A source of phosphatidylinositol 3-phosphate. J Biol Chem. 1998; 273(23):14081-4. DOI: 10.1074/jbc.273.23.14081. View

Fruman D, Meyers R, Cantley L . Phosphoinositide kinases. Annu Rev Biochem. 1998; 67:481-507. DOI: 10.1146/annurev.biochem.67.1.481. View

Bansal V, Caldwell K, MAJERUS P . The isolation and characterization of inositol polyphosphate 4-phosphatase. J Biol Chem. 1990; 265(3):1806-11. View

Cunningham T, Lips D, Bansal V, Caldwell K, Mitchell C, MAJERUS P . Pathway for the formation of D-3 phosphate containing inositol phospholipids in intact human platelets. J Biol Chem. 1990; 265(35):21676-83. View

Stephens L, Hughes K, Irvine R . Pathway of phosphatidylinositol(3,4,5)-trisphosphate synthesis in activated neutrophils. Nature. 1991; 351(6321):33-9. DOI: 10.1038/351033a0. View

Zhang J, Fry M, Waterfield M, Jaken S, Liao L, Fox J . Activated phosphoinositide 3-kinase associates with membrane skeleton in thrombin-exposed platelets. J Biol Chem. 1992; 267(7):4686-92. View

Hawkins P, Jackson T, Stephens L . Platelet-derived growth factor stimulates synthesis of PtdIns(3,4,5)P3 by activating a PtdIns(4,5)P2 3-OH kinase. Nature. 1992; 358(6382):157-9. DOI: 10.1038/358157a0. View

10.

Fry M, Panayotou G, Dhand R, Ruiz-Larrea F, Gout I, Nguyen O . Purification and characterization of a phosphatidylinositol 3-kinase complex from bovine brain by using phosphopeptide affinity columns. Biochem J. 1992; 288 ( Pt 2):383-93. PMC: 1132023. DOI: 10.1042/bj2880383. View

11.

Berridge M . Inositol trisphosphate and calcium signalling. Nature. 1993; 361(6410):315-25. DOI: 10.1038/361315a0. View

12.

Norris F, MAJERUS P . Hydrolysis of phosphatidylinositol 3,4-bisphosphate by inositol polyphosphate 4-phosphatase isolated by affinity elution chromatography. J Biol Chem. 1994; 269(12):8716-20. View

13.

Guinebault C, Payrastre B, Racaud-Sultan C, Mazarguil H, Breton M, Mauco G . Integrin-dependent translocation of phosphoinositide 3-kinase to the cytoskeleton of thrombin-activated platelets involves specific interactions of p85 alpha with actin filaments and focal adhesion kinase. J Cell Biol. 1995; 129(3):831-42. PMC: 2120444. DOI: 10.1083/jcb.129.3.831. View

14.

Kovacsovics T, Bachelot C, Toker A, Vlahos C, Duckworth B, Cantley L . Phosphoinositide 3-kinase inhibition spares actin assembly in activating platelets but reverses platelet aggregation. J Biol Chem. 1995; 270(19):11358-66. DOI: 10.1074/jbc.270.19.11358. View

15.

Norris F, Auethavekiat V, MAJERUS P . The isolation and characterization of cDNA encoding human and rat brain inositol polyphosphate 4-phosphatase. J Biol Chem. 1995; 270(27):16128-33. DOI: 10.1074/jbc.270.27.16128. View

16.

Jackson S, Schoenwaelder S, Matzaris M, Brown S, Mitchell C . Phosphatidylinositol 3,4,5-trisphosphate is a substrate for the 75 kDa inositol polyphosphate 5-phosphatase and a novel 5-phosphatase which forms a complex with the p85/p110 form of phosphoinositide 3-kinase. EMBO J. 1995; 14(18):4490-500. PMC: 394541. DOI: 10.1002/j.1460-2075.1995.tb00128.x. View

17.

Liu L, Jefferson A, Zhang X, Norris F, MAJERUS P, Krystal G . A novel phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase associates with the interleukin-3 receptor. J Biol Chem. 1996; 271(47):29729-33. DOI: 10.1074/jbc.271.47.29729. View

18.

Rittenhouse S . Phosphoinositide 3-kinase activation and platelet function. Blood. 1996; 88(12):4401-14. View

19.

Franke T, Kaplan D, Cantley L, Toker A . Direct regulation of the Akt proto-oncogene product by phosphatidylinositol-3,4-bisphosphate. Science. 1997; 275(5300):665-8. DOI: 10.1126/science.275.5300.665. View

20.

Norris F, Atkins R, MAJERUS P . Inositol polyphosphate 4-phosphatase is inactivated by calpain-mediated proteolysis in stimulated human platelets. J Biol Chem. 1997; 272(17):10987-9. DOI: 10.1074/jbc.272.17.10987. View