Related Experiment Video
Updated: Oct 5, 2026

Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro
Published on: March 17, 2023
Glucagon receptor activates extracellular signal-regulated protein kinase 1/2 via cAMP-dependent protein kinase
Y Jiang1, A M Cypess, E D Muse
1Laboratory of Molecular Biology and Biochemistry, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA.
Abstract:
We prepared a stable cell line expressing the glucagon receptor to characterize the effect of G(s)-coupled receptor stimulation on extracellular signal-regulated protein kinase 1/2 (ERK1/2) activity. Glucagon treatment of the cell line caused a dose-dependent increase in cAMP concentration, activation of cAMP-dependent protein kinase (PKA), and transient release of intracellular calcium. Glucagon treatment also caused rapid dose-dependent phosphorylation and activation of mitogen-activated protein kinase kinase/ERK kinase (MEK1/2) and ERK1/2. Inhibition of either PKA or MEK1/2 blocked ERK1/2 activation by glucagon. However, no significant activation of several upstream activators of MEK, including Ras, Rap1, and Raf, was observed in response to glucagon treatment. In addition, chelation of intracellular calcium reduced glucagon-mediated ERK1/2 activation. In transient transfection experiments, glucagon receptor mutants that bound glucagon but failed to increase intracellular cAMP and calcium concentrations showed no glucagon-stimulated ERK1/2 phosphorylation. We conclude that glucagon-induced MEK1/2 and ERK1/2 activation is mediated by PKA and that an increase in intracellular calcium concentration is required for maximal ERK activation.
Related Concept Videos
cAMP-dependent Protein Kinase Pathways
GPCRs Regulate Adenylyl Cylase Activity
Two...
Insulin: The Receptor and Signaling Pathways
Amplifying Signals via Enzymatic Cascade
Intracellular Signaling Cascades
PI3K/mTOR/AKT Signaling Pathway
