Adenylyl cyclase signaling mechanisms of relaxin and insulin action: similarities and differences.
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 ==>G(i) protein (betagamma-dimer) ==>phosphatidylinositol 3-kinase ==>protein kinase Czeta ==>G(s) 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.
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Thorez pr. 44, 194223, St. Petersburg, Russia. sveta@iephb.ru
Marianna
M
Pertseva
Alexander
A
Shpakov
Ludmila
L
Kuznetsova
Svetlana
S
Plesneva
Evgeniya
E
Omeljaniuk
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D009215:Myometrium / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011247:Pregnancy; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012065:Relaxin / Q000378:metabolism*; D015398:Signal Transduction; D000099221:Protein Kinase C zeta
D000262:Adenylyl Cyclases; D002772:Cholera Toxin; D019204:GTP-Binding Proteins; D007328:Insulin; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D020794:Receptor Protein-Tyrosine Kinases; D012065:Relaxin; D000099221:Protein Kinase C zeta