Adenylate cyclase factor

J (339), a 28-amino acid peptide, is a member of a family of stmctuially related peptides that includes secretin [1393-25-5] (340), growth hormone releasing factor (GRF), and pituitary adenylate cyclase-activating peptide (PACAP) [137061(341) (83). 

Adenylate cyclase was identified as the primary Ras target in yeast (Saccha-romyces cerevisiae) [56] but it took a while before in 1993 several groups independently found Raf to be the effector of Ras in mammals [41-44]. Shortly afterwards it was realized that this is not the only target of Ras but up until now it appears to be the most prominent one. Raf is a Ser/Thr-specific protein kinase which phosphorylates and thereby activates Mek which in turn phosphorylates and activates Erk, leading to an amplification of the signal. Erk, also termed MAPK, has a plethora of phosphorylation targets, the most important of which are transcription factors such as Elk-1, leading to activation of the transcription machinery in the nucleus. 

Although details will vary, in each case an agonist at its receptor activates adenylate cyclase and the second messenger cAMP is produced from ATP. cAMP activates protein kinase A and a cascade of reactions may follow. These may be metabolic reactions, as in the cases just described, or activation of a cAMP response-element protein, CREB. CREB is a transcription factor with affinity for specific sites on DNA. Control of protein synthesis follows. 

Chen F, Bilezikjian LM, Perrin MH, Rivier J, Vale W (1986) Corticotropin releasing factor receptor-mediated stimulation of adenylate cyclase activity in the rat brain. Brain Res 381 49-57... 

Pihoker C, Cain ST, Nemeroff CB. Postnatal development of regional binding of corticotropin-releasing factor and adenylate cyclase activity in the rat brain. Prog Neuro-Psychopharm Biol Psychiatry 1992 16 581-586. 

Since cyclic AMP derivatives and inhibitors of cyclic nucleotide phosphodiesterase stimulate prolactin release (17, 37, 38) and dopamine is a potent inhibitor of prolactin secretion (1, ly 39), it is not surprising that the catecholamine does not stimulate the adenylate cyclase system. On the contrary, the data summarized above show that the pituitary DA receptor is negatively coupled to adenylate cyclase. The pituitary DA receptor is thus a typical DA -receptor (40, 41). In view of the multiplicity of factors involved in the control of prolactin secretion, including sex steroids, it is likely that mechanisms other than cyclic AMP are involved (39, 42). It does however appear that inhibition of cyclic AMP formation by dopamine is a key element in a multifactorial control system responsible for the fine tuning of prolactin secretion. 

Corticotropin-releasing factor stimulates adenylate cyclase in the intermediate lobe of the pituitary gland... 

---