Cellular Localization and Characterization of Cytosolic Binding Partners for Gla Domain-containing Proteins PRRG4 and PRRG2

The genes encoding a family of proteins termed proline-rich γ-carboxyglutamic acid (PRRG) proteins were identified and characterized more than a decade ago, but their functions remain unknown. These novel membrane proteins have an extracellular γ-carboxyglutamic acid (Gla) protein domain and cytosolic WW binding motifs. We screened WW domain arrays for cytosolic binding partners for PRRG4 and identified novel protein-protein interactions for the protein. We also uncovered a new WW binding motif in PRRG4 that is essential for these newly found protein-protein interactions. Several of the PRRG-interacting proteins we identified are essential for a variety of physiologic processes. Our findings indicate possible novel and previously unidentified functions for PRRG proteins.Background: PRRG proteins were cloned more than a decade ago, but their function is still not known.Results: Several novel protein-protein interactions for PRRG are identified by array screening and pulldown analysis.Conclusion: PRRG-initiated signaling events most likely depend on proteins with WW domains.Significance: The protein-protein interactions identified here may help to elucidate the roles of PRRG proteins in different physiological settings. The genes encoding a family of proteins termed proline-rich γ-carboxyglutamic acid (PRRG) proteins were identified and characterized more than a decade ago, but their functions remain unknown. These novel membrane proteins have an extracellular γ-carboxyglutamic acid (Gla) protein domain and cytosolic WW binding motifs. We screened WW domain arrays for cytosolic binding partners for PRRG4 and identified novel protein-protein interactions for the protein. We also uncovered a new WW binding motif in PRRG4 that is essential for these newly found protein-protein interactions. Several of the PRRG-interacting proteins we identified are essential for a variety of physiologic processes. Our findings indicate possible novel and previously unidentified functions for PRRG proteins. Background: PRRG proteins were cloned more than a decade ago, but their function is still not known. Results: Several novel protein-protein interactions for PRRG are identified by array screening and pulldown analysis. Conclusion: PRRG-initiated signaling events most likely depend on proteins with WW domains. Significance: The protein-protein interactions identified here may help to elucidate the roles of PRRG proteins in different physiological settings.