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PMID: 11802782 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Evidence that the tandem-pleckstrin-homology-domain-containing protein TAPP1 interacts with Ptd(3,4)P2 and the multi-PDZ-domain-containing protein MUPP1 in vivo.

The Biochemical journal ·Vol. 361 ·No. Pt 3 ·2002-02-01 ·Pages 525-36

Kimber WA, Trinkle-Mulcahy L, Cheung PC, Deak M, Marsden LJ, Kieloch A, Watt S, Javier RT, Gray A, Downes CP, Lucocq JM, Alessi DR

Abstract

PtdIns(3,4,5)P3 is an established second messenger of growth-factor and insulin-induced signalling pathways. There is increasing evidence that one of the immediate breakdown products of PtdIns(3,4,5)P3, namely PtdIns(3,4)P2, whose levels are elevated by numerous extracellular agonists, might also function as a signalling molecule. Recently, we identified two related pleckstrin-homology (PH)-domain-containing proteins, termed 'tandem-PH-domain-containing protein-1' (TAPP1) and TAPP2, which interacted in vitro with high affinity with PtdIns(3,4)P2, but did not bind PtdIns(3,4,5)P3 or other phosphoinositides. In the present study we demonstrate that stimulation of Swiss 3T3 or 293 cells with agonists that stimulate PtdIns(3,4)P2 production results in the marked translocation of TAPP1 to the plasma membrane. This recruitment is dependent on a functional PtdIns(3,4)P2-binding PH domain and is inhibited by wortmannin, a phosphoinositide 3-kinase inhibitor that prevents PtdIns(3,4)P2 generation. A search for proteins that interact with TAPP1 identified the multi-PDZ-containing protein termed 'MUPP1', a protein possessing 13 PDZ domains and no other known modular or catalytic domains [PDZ is postsynaptic density protein (PSD-95)/Drosophila disc large tumour suppressor (dlg)/tight junction protein (ZO1)]. We demonstrate that immunoprecipitation of endogenously expressed TAPP1 from 293-cell lysates results in the co-immunoprecipitation of endogenous MUPP1, indicating that these proteins are likely to interact with each other physiologically. We show that TAPP1 and TAPP2 interact with the 10th and 13th PDZ domain of MUPP1 through their C-terminal amino acids. The results of the present study suggest that TAPP1 and TAPP2 could function in cells as adapter proteins to recruit MUPP1, or other proteins that they may interact with, to the plasma membrane in response to signals that elevate PtdIns(3,4)P2.

MeSH Terms
Animals Bacterial Proteins/metabolism Blood Proteins/chemistry Carrier Proteins/chemistry,metabolism Cell Line Cell Membrane/metabolism Cloning, Molecular Fibroblasts/metabolism Genetic Vectors Glutathione Transferase/metabolism Humans Hydrogen Peroxide/pharmacology Immunoblotting Immunohistochemistry Intracellular Signaling Peptides and Proteins Luminescent Proteins/metabolism Membrane Proteins Mice Microscopy, Immunoelectron Oxidative Stress Phosphatidylinositol 3-Kinases/metabolism Phosphatidylinositol Phosphates/metabolism Phosphoproteins/chemistry Precipitin Tests Protein Binding Protein Structure, Tertiary Recombinant Fusion Proteins/metabolism Time Factors Two-Hybrid System Techniques
Chemicals
Bacterial Proteins Blood Proteins Carrier Proteins Intracellular Signaling Peptides and Proteins Luminescent Proteins MPDZ protein, human Membrane Proteins Mpdz protein, mouse PLEKHA1 protein, human Phosphatidylinositol Phosphates Phosphoproteins Recombinant Fusion Proteins phosphatidylinositol 3,4-diphosphate platelet protein P47 yellow fluorescent protein, Bacteria Hydrogen Peroxide Glutathione Transferase Phosphatidylinositol 3-Kinases
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Kimber Wendy A
MRC Protein Phosphorylation Unit, MSI/WTB Complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK. w.a.kimber@dundee.ac.uk
Trinkle-Mulcahy Laura
Cheung Peter C F
Deak Maria
Marsden Louisa J
Kieloch Agnieszka
Watt Stephen
Javier Ronald T
Gray Alex
Downes C Peter
Lucocq John M
Alessi Dario R
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/0264-6021:3610525
Email
w.a.kimber@dundee.ac.uk
Published
2002-02-01
Pages
525-36
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1222335
Subset
IM
Grants
NCI NIH HHS · R01 CA058541 · United States
External Links
PubMed source DOI: 10.1042/0264-6021:3610525 PMC Full Text View journal details
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