PMID- 10097090
OWN - NLM
STAT- MEDLINE
DCOM- 19990512
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 7
DP  - 1999 Mar 30
TI  - The inositol polyphosphate 4-phosphatase forms a complex with
      phosphatidylinositol 3-kinase in human platelet cytosol.
PG  - 3640-5
AB  - 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.
FAU - Munday, A D
AU  - Munday AD
AD  - Department of Biochemistry and Molecular Biology, Monash University, Clayton
      Campus, Clayton 3168, Victoria, Australia.
FAU - Norris, F A
AU  - Norris FA
FAU - Caldwell, K K
AU  - Caldwell KK
FAU - Brown, S
AU  - Brown S
FAU - Majerus, P W
AU  - Majerus PW
FAU - Mitchell, C A
AU  - Mitchell CA
LA  - eng
GR  - HL 55672/HL/NHLBI NIH HHS/United States
GR  - HL 07088/HL/NHLBI NIH HHS/United States
GR  - R01 HL016634/HL/NHLBI NIH HHS/United States
GR  - R01 HL055672/HL/NHLBI NIH HHS/United States
GR  - T32 HL007088/HL/NHLBI NIH HHS/United States
GR  - HL 16634/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Macromolecular Substances)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - EC 3.1.3.66 (phosphatidylinositol-3,4-bisphosphate 4-phosphatase)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
MH  - Blood Platelets/drug effects/*enzymology
MH  - Cytosol/enzymology
MH  - Humans
MH  - Kinetics
MH  - Macromolecular Substances
MH  - Phosphatidylinositol 3-Kinases/*blood/chemistry/isolation & purification
MH  - Phosphoric Monoester Hydrolases/*blood/isolation & purification
MH  - Thrombin/pharmacology
PMC - PMC22347
EDAT- 1999/03/31 00:00
MHDA- 1999/03/31 00:01
CRDT- 1999/03/31 00:00
PHST- 1999/03/31 00:00 [pubmed]
PHST- 1999/03/31 00:01 [medline]
PHST- 1999/03/31 00:00 [entrez]
AID - 10.1073/pnas.96.7.3640 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3640-5. doi: 10.1073/pnas.96.7.3640.