Dissociation of SHP-1 from spinophilin during platelet activation exposes an inhibitory binding site for protein phosphatase-1 (PP1)

PloS One
Peisong MaLawrence F Brass

Abstract

We have recently shown that a critical regulatory node in the platelet signaling network lies immediately downstream of platelet receptors for thrombin and TxA2. This node is comprised of a scaffold protein (spinophilin, SPL), a protein tyrosine phosphatase (SHP-1), and either of the two members of the Regulators of G protein Signaling family predominantly expressed in platelets (RGS10 or RGS18). The SPL/RGS/SHP-1 complex is present in resting platelets, dissociating when thrombin or TxA2, but not ADP or collagen, activate SHP-1 and release RGS10 and RGS18 to dampen signaling. Here we demonstrate an additional regulatory role for spinophilin, showing that dissociation of SHP-1 from spinophilin is followed by an increase in the binding of spinophilin to PP1, a serine/threonine phosphatase whose binding site maps to a region close to the SHP-1 binding site. The increase in PP1 binding to spinophilin is limited to platelet agonists that cause dissociation of the complex and is selective for the α and γ isoforms of PP1. Studies in cell culture show that SHP-1 and PP1 can compete for binding to spinophilin and that binding inhibits PP1 activity since over-expression of wild type spinophilin, but not spinophilin with a disabled PP1 b...Continue Reading

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Citations

May 15, 2015·Biochemical and Biophysical Research Communications·Fatima Z AlshboolFadi T Khasawneh
Feb 17, 2017·Biochemical Society Transactions·Iris VerbinnenMathieu Bollen
Sep 27, 2015·Blood·Peisong MaLawrence F Brass
Jul 27, 2018·Research and Practice in Thrombosis and Haemostasis·Zoltan Nagy, Albert Smolenski
Aug 1, 2020·International Journal of Molecular Sciences·Xi ChenPeisong Ma
May 28, 2020·Frontiers in Cell and Developmental Biology·Chenxi WangQiang Sun
Dec 15, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Alessandra V S FariaGwenny M Fuhler

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Methods Mentioned

BETA
PCR
transfection
electrophoresis
immunoprecipitation
Precipitation

Software Mentioned

NIH ImageJ

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