Adenylyl cyclase signaling mechanisms of relaxin and insulin action: Similarities and differences

Authors

  • Marianna Pertseva,

    Corresponding author
    1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Thorez pr. 44, 194223, St. Petersburg, Russia
    Search for more papers by this author
  • Alexander Shpakov,

    1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Thorez pr. 44, 194223, St. Petersburg, Russia
    Search for more papers by this author
  • Ludmila Kuznetsova,

    1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Thorez pr. 44, 194223, St. Petersburg, Russia
    Search for more papers by this author
  • Svetlana Plesneva,

    1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Thorez pr. 44, 194223, St. Petersburg, Russia
    Search for more papers by this author
  • Evgeniya Omeljaniuk

    1. Ott Institute of Obstetrics and Gynecology, Russian Academy of Medical Sciences, Mendeleev line 3, 199034, St. Petersburg, Russia
    Search for more papers by this author

Corresponding author. Fax: +7 (812) 552 3012. sveta@iephb.ru

Abstract

The adenylyl cyclase signaling mechanism (ACSM) of relaxin H2 action was discovered and deciphered in mammalian muscles. A study of signaling blocks involved in ACSM of relaxin in comparison with that of insulin previously detected showed a close similarity throughout the post-receptor signaling chain of both hormones. The inhibitory action of tyrosine kinase blockers on the hormone AC activating effect indicates that the relaxin receptor involved in ACSM is likely to be of the tyrosine kinase type. However, a recent discovery of a relaxin receptor with serpentine architecture leaves open the question concerning the existence of receptor of the tyrosine kinase type. The structural-functional organization of the ACSM due to the action of relaxin—shown here for the first time—can be presented as the following signaling sequence: relaxin receptor ⇒ Gi protein (βγ-dimer) ⇒ phosphatidylinositol 3-kinase ⇒ protein kinase Cζ ⇒ Gs protein ⇒ adenylyl cyclase. According to our hypothesis, the regulatory action of the insulin superfamily peptides on cell processes (proliferation, apoptosis, and metabolism) is mediated via ACSM.

Ancillary