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PMID:14516276

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Citation

Kimber, WA, Deak, M, Prescott, AR and Alessi, DR (2003) Interaction of the protein tyrosine phosphatase PTPL1 with the PtdIns(3,4)P2-binding adaptor protein TAPP1. Biochem. J. 376:525-35

Abstract

It has been postulated that PtdIns(3,4) P (2), one of the immediate breakdown products of PtdIns(3,4,5) P (3), functions as a signalling molecule in insulin- and growth-factor-stimulated pathways. To date, the t andem- P H-domain-containing p rotein- 1 (TAPP1) and related TAPP2 are still the only known PH-domain-containing proteins that interact strongly and specifically with PtdIns(3,4) P (2). In this study we demonstrate that endogenously expressed TAPP1, is constitutively associated with the protein-tyrosine-phosphatase-like protein-1 (PTPL1 also known as FAP-1). We show that PTPL1 binds to TAPP1 and TAPP2, principally though its first PDZ domain [where PDZ is postsynaptic density protein ( P SD-95)/ Drosophila disc large tumour suppressor ( d lg)/tight junction protein ( Z O1)] and show that this renders PTPL1 capable of associating with PtdIns(3,4) P (2) in vitro. Our data suggest that the binding of TAPP1 to PTPL1 does not influence PTPL1 phosphatase activity, but instead functions to maintain PTPL1 in the cytoplasm. Following stimulation of cells with hydrogen peroxide to induce PtdIns(3,4) P (2) production, PTPL1, complexed to TAPP1, translocates to the plasma membrane. This study provides the first evidence that TAPP1 and PtdIns(3,4) P (2) could function to regulate the membrane localization of PTPL1. We speculate that if PTPL1 was recruited to the plasma membrane by increasing levels of PtdIns(3,4) P (2), it could trigger a negative feedback loop in which phosphoinositide-3-kinase-dependent or other signalling pathways could be switched off by the phosphatase-catalysed dephosphorylation of receptor tyrosine kinases or tyrosine phosphorylated adaptor proteins such as IRS1 or IRS2. Consistent with this notion we observed RNA-interference-mediated knock-down of TAPP1 in HEK-293 cells, enhanced activation and phosphorylation of PKB following IGF1 stimulation.

Links

PubMed PMC1223793 Online version:10.1042/BJ20031154

Keywords

Carrier Proteins/genetics; Carrier Proteins/metabolism; Carrier Proteins/physiology; Cell Line; Humans; Intracellular Signaling Peptides and Proteins; Membrane Proteins/genetics; Membrane Proteins/metabolism; Membrane Proteins/physiology; Phosphatidylinositol Phosphates/metabolism; Phosphorylation; Protein Structure, Tertiary; Protein Tyrosine Phosphatase, Non-Receptor Type 13; Protein Tyrosine Phosphatases/analysis; Protein Tyrosine Phosphatases/chemistry; Protein Tyrosine Phosphatases/metabolism; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-akt; RNA Interference

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:PTN13

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9ERS5

F

Seeded From UniProt

complete

HUMAN:PTN13

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9HB21

F

Seeded From UniProt

complete

HUMAN:PTN13

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PTN13

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PKHA2

enables

GO:0030165: PDZ domain binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q12923

F

Seeded From UniProt

complete

HUMAN:PKHA1

enables

GO:0030165: PDZ domain binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q12923

F

Seeded From UniProt

complete

HUMAN:PKHA1

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PKHA1

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PKHA1

involved_in

GO:0051898: negative regulation of protein kinase B signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PKHA1

involved_in

GO:0070301: cellular response to hydrogen peroxide

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PKHA1

involved_in

GO:0045184: establishment of protein localization

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PTN13

part_of

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PTN13

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PTN13

enables

GO:0004725: protein tyrosine phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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