The type Ialpha inositol polyphosphate 4-phosphatase generates and terminates phosphoinositide 3-kinase signals on endosomes and the plasma membrane.
Endosomal trafficking is regulated by the recruitment of effector proteins to phosphatidylinositol 3-phosphate [PtdIns(3)P] on early endosomes. At the plasma membrane, phosphatidylinositol-(3,4)-bisphosphate [PtdIns(3,4)P2] binds the pleckstrin homology (PH) domain-containing proteins Akt and TAPP1. Type Ialpha inositol polyphosphate 4-phosphatase (4-phosphatase) dephosphorylates PtdIns(3,4)P2, forming PtdIns(3)P, but its subcellular localization is unknown. We report here in quiescent cells, the 4-phosphatase colocalized with early and recycling endosomes. On growth factor stimulation, 4-phosphatase endosomal localization persisted, but in addition the 4-phosphatase localized at the plasma membrane. Overexpression of the 4-phosphatase in serum-stimulated cells increased cellular PtdIns(3)P levels and prevented wortmannin-induced endosomal dilatation. Furthermore, mouse embryonic fibroblasts from homozygous Weeble mice, which have a mutation in the type I 4-phosphatase, exhibited dilated early endosomes. 4-Phosphatase translocation to the plasma membrane upon growth factor stimulation inhibited the recruitment of the TAPP1 PH domain. The 4-phosphatase contains C2 domains, which bound PtdIns(3,4)P2, and C2-domain-deletion mutants lost PtdIns(3,4)P2 4-phosphatase activity, did not localize to endosomes or inhibit TAPP1 PH domain membrane recruitment. The 4-phosphatase therefore both generates and terminates phosphoinositide 3-kinase signals at distinct subcellular locations.
Ivetac
Ivan
I
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia 3800.
Munday
Adam D
AD
Kisseleva
Marina V
MV
Zhang
Xiang-Ming
XM
Luff
Susan
S
Tiganis
Tony
T
Whisstock
James C
JC
Rowe
Tony
T
Majerus
Phillip W
PW
Mitchell
Christina A
CA
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D016466:CHO Cells; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006224:Cricetinae; D011992:Endosomes / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D015398:Signal Transduction; D014162:Transfection; D000077191:Wortmannin; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
D000730:Androstadienes; D004815:Epidermal Growth Factor; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010744:Phosphoric Monoester Hydrolases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins; D000077191:Wortmannin; D020691:rab GTP-Binding Proteins; C435927:PLEKHA1 protein, human; C055525:phosphatidylinositol 3-phosphate; C494918:AKT1 protein, human; C053153:phosphatidylinositol-3,4-bisphosphate 4-phosphatase
J Biol Chem. 1998 Jan 2;273(1):13-6
9417038
J Biol Chem. 1997 Sep 19;272(38):23859-64
9295334
Proc Natl Acad Sci U S A. 1998 May 26;95(11):6187-92
9600939
Nature. 1998 Jul 30;394(6692):494-8
9697774
Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14057-9
9826652
J Biol Chem. 1998 Dec 11;273(50):33379-85
9837914
EMBO Rep. 2001 Jan;2(1):68-74
11252727
Nat Cell Biol. 2001 Jul;3(7):675-8
11433300
Curr Opin Cell Biol. 2001 Aug;13(4):485-92
11454456
J Cell Biol. 2001 Sep 17;154(6):1197-208
11564757
Neuron. 2001 Oct 25;32(2):203-12
11683991
J Cell Biol. 2001 Dec 10;155(6):1065-79
11739414
J Biol Chem. 2002 Feb 22;277(8):6266-72
11706019
Mol Cell. 2002 Feb;9(2):205-6
11864591
J Biol Chem. 2002 Mar 15;277(11):9027-35
11781306
IUBMB Life. 2002 Jan;53(1):25-36
12018404
Science. 2002 May 31;296(5573):1655-7
12040186
Mol Cell Biol. 2002 Aug;22(15):5479-91
12101241
Annu Rev Physiol. 2003;65:791-815
12518000
J Biol Chem. 2003 Mar 28;278(13):11376-85
12536145
Traffic. 2003 Apr;4(4):201-13
12694559
Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7491-6
12808147
Histochem Cell Biol. 2003 Dec;120(6):445-53
14618335
Biochem J. 2004 Feb 1;377(Pt 3):653-63
14604433
Trends Biochem Sci. 2004 Mar;29(3):143-51
15003272
Nat Rev Mol Cell Biol. 2004 Feb;5(2):121-32
15040445
J Biol Chem. 2004 Oct 8;279(41):43027-34
15292201
J Cell Biol. 1987 Sep;105(3):1253-65
3308906
J Biol Chem. 1991 Sep 25;266(27):18378-86
1655747
Biochim Biophys Acta. 1993 Oct 7;1179(1):27-75
8399352
J Biol Chem. 1995 Jul 7;270(27):16128-33
7608176
Biochem J. 1995 Oct 1;311 ( Pt 1):31-4
7575470
Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10207-11
7479754
Cell. 1999 Oct 29;99(3):323-34
10555148
Nat Cell Biol. 1999 Aug;1(4):249-52
10559924
J Biol Chem. 1999 Dec 10;274(50):35963-8
10585485
Mol Biol Cell. 2000 Feb;11(2):467-80
10679007
J Biol Chem. 2000 Apr 21;275(16):11943-50
10766823
Mol Cell. 2000 Aug;6(2):373-84
10983984
Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13696-701
11087841
J Cell Biol. 2000 Dec 11;151(6):1207-20
11121436
Biochem J. 2000 Oct 1;351(Pt 1):19-31
11001876
Curr Opin Cell Biol. 2001 Apr;13(2):146-52
11248547
J Cell Biol. 1996 Jan;132(1-2):21-33
8567724
Arch Biochem Biophys. 1996 Feb 1;326(1):64-72
8579373
J Biol Chem. 1996 Sep 27;271(39):24048-54
8798641
J Biol Chem. 1997 Apr 25;272(17):10987-9
9110986
Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7326-30
9207090
Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
9254694
Mol Biol Cell. 1998 Feb;9(2):323-32
9450958