The E92K Melanocortin 1 Receptor Mutant Induces cAMP Production and Arrestin Recruitment but Not ERK Activity Indicating Biased Constitutive Signaling
2011

The E92K Melanocortin 1 Receptor Mutant Induces cAMP Production and Arrestin Recruitment but Not ERK Activity Indicating Biased Constitutive Signaling

publication Evidence: moderate

Author Information

Author(s): Benned-Jensen, Tau Mokrosinski, Jacek Rosenkilde, Mette M. Rosenkilde

Primary Institution: University of Copenhagen

Hypothesis

The E92K mutation in the melanocortin 1 receptor (MC1R) induces biased constitutive signaling.

Conclusion

The E92K mutation leads to increased cAMP production and β-arrestin recruitment without activating ERK1/2, indicating a biased signaling mechanism.

Supporting Evidence

  • The E92K mutation significantly increases cAMP accumulation.
  • The E92K mutant shows enhanced β-arrestin recruitment.
  • The mutation does not lead to ERK1/2 activation.
  • The study suggests a unique role for the extracellular loop 1 in receptor activation.

Takeaway

A change in a specific part of a protein can make it work differently, helping us understand how some animals have darker fur.

Methodology

The study involved characterizing the constitutive activity, cell surface expression, and internalization of the Mc1r E92K mutant using HEK293 cells.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0024644

Want to read the original?

Access the complete publication on the publisher's website

View Original Publication