Intra- and intermolecular interactions between intracellular domains of receptor protein-tyrosine phosphatases.
The presence of two protein-tyrosine phosphatase (PTP) domains is a striking feature in most transmembrane receptor PTPs (RPTPs). The generally inactive membrane-distal PTP domains (RPTP-D2s) bind and are proposed to regulate the membrane-proximal PTP domains (RPTP-D1s). We set out to characterize the interactions between RPTP-D1s and RPTP-D2s in vivo by ... co-immunoprecipitation of hemagglutinin-tagged fusion proteins encoding the transmembrane domain and RPTP-D1 and myc-tagged RPTP-D2. Seven RPTPs from four different subfamilies were used: RPTPalpha, RPTPepsilon, LAR, RPTPvarsigma, RPTPdelta, CD45, and RPTP(mu). We found that RPTP-D2s bound to RPTPs with different affinities. The presence of intrinsic RPTP-D2 altered the binding specificity toward other RPTP-D2s positively or negatively, depending on the identity of the RPTPs. Furthermore, the C terminus of RPTP-D2s and the "wedge" in RPTP-D1s played a central role in binding specificity. Finally, full-length RPTPalpha and LAR heterodimerized in an oxidative stress-dependent manner. Like RPTPalpha-D2, the LAR-D2 conformation was affected by oxidative stress, suggesting a common regulatory mechanism for RPTP complex formation. Taken together, interactions between RPTP-D1s and RPTP-D2s are a common but specific mechanism that is likely to be regulated. The RPTP-D2s and the wedge structures are crucial determinants of binding specificity, thus regulating cross-talk between RPTPs.
Mesh Terms:
Amino Acid Sequence, Binding Sites, Cell Line, Cell Membrane, Dimerization, Energy Transfer, Humans, Hydrogen Peroxide, Immunoblotting, Leukocyte Common Antigens, Molecular Sequence Data, Oxygen, Precipitin Tests, Protein Binding, Protein Conformation, Protein Structure, Tertiary, Protein Tyrosine Phosphatases, Receptor-Like Protein Tyrosine Phosphatases, Class 2, Receptor-Like Protein Tyrosine Phosphatases, Class 4, Receptors, Cell Surface, Spectrometry, Fluorescence, Transfection
Amino Acid Sequence, Binding Sites, Cell Line, Cell Membrane, Dimerization, Energy Transfer, Humans, Hydrogen Peroxide, Immunoblotting, Leukocyte Common Antigens, Molecular Sequence Data, Oxygen, Precipitin Tests, Protein Binding, Protein Conformation, Protein Structure, Tertiary, Protein Tyrosine Phosphatases, Receptor-Like Protein Tyrosine Phosphatases, Class 2, Receptor-Like Protein Tyrosine Phosphatases, Class 4, Receptors, Cell Surface, Spectrometry, Fluorescence, Transfection
J. Biol. Chem.
Date: Dec. 06, 2002
PubMed ID: 12376545
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