Direct interaction between ER membrane-bound PTP1B and its plasma membrane-anchored targets.
The ubiquitously expressed protein tyrosine phosphatase PTP1B is involved in the regulation of numerous cellular signaling pathways. PTP1B is anchored to the ER membrane while many of its substrates are localized to the plasma membrane. This spatial separation raises the question how PTP1B can interact with its targets. In our study we demonstrate direct interaction of PTP1B with the Ser/Thr kinase PKCdelta, the non-receptor tyrosine kinase Src and the insulin receptor which all are key enzymes in cellular signaling cascades. Protein complex formation was visualized in vivo using Bimolecular Fluorescence Complementation (BiFC). We demonstrate that complex formation of PTP1B with plasma membrane-anchored proteins is possible without detachment of PTP1B from the ER. Our data indicate that the dynamic ER membrane network is in constant contact to the plasma membrane. Local attachments of the two membrane systems enable a direct communication of ER- and plasma membrane-anchored proteins. The reported formation of membrane junctions is an important step towards the understanding of signal transmissions between the ER and the plasma membrane.
Anderie
Ines
I
Department of Physiology, University of the Saarland, D-66421, Homburg/Saar, Germany.
Schulz
Irene
I
Schmid
Andreas
A
D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D018613:Microscopy, Confocal; D008954:Models, Biological; D051745:Protein Kinase C-delta / Q000378:metabolism*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D011972:Receptor, Insulin; D051745:Protein Kinase C-delta; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases