A protein interaction network centered on leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) regulates growth factor receptors
| Autor: | Camilla Holmlund, Carl Herdenberg, Roger Henriksson, Mahmood Faraz, Håkan Hedman |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
platelet-derived growth factor-C (PDGF-C) yeast two-hybrid Two-hybrid screening Intracellular Space Leucine-rich repeat Biochemistry Receptor tyrosine kinase law.invention Protein–protein interaction protein-protein interaction 03 medical and health sciences Growth factor receptor Interaction network law Humans Receptors Growth Factor Protein Interaction Maps PON2 Molecular Biology protein expression PDGFRA PON2 PTPRK Cancer och onkologi Membrane Glycoproteins biology Chemistry LRIG1 Cell Biology Cell biology Transport protein ZBTB16 PDGFRA Protein Transport 030104 developmental biology Cancer and Oncology biology.protein receptor tyrosine kinase Suppressor Signal Transduction |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X |
| Popis: | Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a tumor suppressor and a negative regulator of several receptor tyrosine kinases. The molecular mechanisms by which LRIG1 mediates its tumor suppressor effects and regulates receptor tyrosine kinases remain incompletely understood. Here, we performed a yeast two-hybrid screen to identify novel LRIG1-interacting proteins and mined data from the BioPlex (biophysical interactions of ORFeome-based complexes) protein interaction data repository. The putative LRIG1 interactors identified in the screen were functionally evaluated using a triple co-transfection system in which HEK293 cells were co-transfected with platelet-derived growth factor receptor α, LRIG1, and shRNAs against the identified LRIG1 interactors. The effects of the shRNAs on the ability of LRIG1 to down-regulate platelet-derived growth factor receptor α expression were evaluated. On the basis of these results, we present an LRIG1 protein interaction network with many newly identified components. The network contains the apparently functionally important LRIG1-interacting proteins RAB4A, PON2, GAL3ST1, ZBTB16, LRIG2, CNPY3, HLA-DRA, GML, CNPY4, LRRC40, and LRIG3, together with GLRX3, PTPRK, and other proteins. In silico analyses of The Cancer Genome Atlas data sets revealed consistent correlations between the expression of the transcripts encoding LRIG1 and its interactors ZBTB16 and PTPRK and inverse correlations between the transcripts encoding LRIG1 and GLRX3. We further studied the LRIG1 function–promoting paraoxonase PON2 and found that it co-localized with LRIG1 in LRIG1-transfected cells. The proposed LRIG1 protein interaction network will provide leads for future studies aiming to understand the molecular functions of LRIG1 and the regulation of growth factor signaling. |
| Databáze: | OpenAIRE |
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