Background:The signaling and regulatory mechanism of the orphan receptor VLGR1 remains elusive. Results: The cleaved VLGR1 -subunit constitutively coupled to G␣ i and was regulated by the VLGR1 ␣-subunit, a diseaseassociated mutation, and PDZD7. Conclusion: The VLGR1 -subunit signals independently and is regulated at multiple levels. Significance: The identified new signaling mechanism may aid in the design of a VLGR1-targeted therapy.
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