Mechanism of glucagon activation of adenylate cyclase in the presence of Mn2+

FEBS Letters

Heyworth, Clare M.¹  Houslay, Miles D.¹  Whetton, Anthony D.² 

[1]Department of Biochemistry and Applied Molecular Biology, University of Manchester Institute of Science and Technology, PO Box 88, Manchester M6O 1QD, England

[2]Paterson Laboratories, Christie Hospital and Hold Radium Institute, Manchester M2O 9BX, England

关键词: Adenylate cyclase;    Glucagon;    Mn2+;    Guanine nucleotide;    Receptor coupling;   

DOI  :  10.1016/0014-5793(82)80627-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

For a variety of ligand states, adenylate cyclase activity in the presence of Mn²⁺ was greater than with Mg²⁺. Trypsin treatment of intact hepatocytes, under conditions which destroy cell surface glucagon receptors, led to a first order loss of glucagon-stimulated adenylate cyclase activity in isolated membranes assayed in the presence of Mn²⁺ whether or not GTP (100 μM) was present in the assays. Arrhenius plots of basal activity exhibited a break at around 22°C, those with NaF were linear and those with glucagon ± GTP (100 μM) were biphasic with a break at around 28°C. It is suggested that Mn²⁺ perturbs the coupling interaction between the glucagon receptor and catalytic unit of adenylate cyclase at the level of the guanine nucleotide regulatory protein. This appears to take the form of Mn²⁺ preventing GTP from initiating glucagon's activation of adenylate cyclase through a collision coupling mechanism.

【 授权许可】

Unknown