title: Forskolin-resistant Y1 adrenal cell mutants are deficient in adenylyl cyclase type 4.
abstract: Four mutant clones independently derived from the Y1 mouse adrenocortical tumor cell line have adenylyl cyclase (AC) activities that are resistant to forskolin, a direct activator of AC. In this study the AC isoform composition of the forskolin-resistant mutants was examined in order to explore the underlying basis for the resistance to forskolin. As determined by Western blot and RT-PCR analysis, the four forskolin-resistant mutants all were deficient in AC-4; the levels of other AC isoforms (AC-1, AC-3 and AC-5/6) were comparable to the levels in parent Y1 cells. Transfection of one of the mutant clones with an AC-4 expression vector increased forskolin-stimulated cAMP signaling, and restored forskolin-induced changes in cell morphology and growth. Taken together, these observations indicate that AC-4 deficiency is a hallmark of the forskolin-resistant phenotype of these mutants and suggest that AC-4 is an important target of forskolin action in the Y1 adrenal cell line.
authors.affiliation: Department of Pharmacology, University of Toronto, Toronto, Ont., Canada M5G 1L6.
authors.forename: Abdallah
authors.initials: A
authors.lastname: Al-Hakim
authors.forename: Xianliang
authors.initials: X
authors.lastname: Rui
authors.forename: Jennivine
authors.initials: J
authors.lastname: Tsao
authors.forename: Paul R
authors.initials: PR
authors.lastname: Albert
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Schimmer
mesh_terms: D000262:Adenylyl Cyclases / Q000032:analysis / Q000172:deficiency* / Q000502:physiology; D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000473:pathology*; D000818:Animals; D002455:Cell Division; D045744:Cell Line, Tumor; D048429:Cell Size; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D051379:Mice; D009154:Mutation; D020033:Protein Isoforms / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D005576:Colforsin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C406262:adenylyl cyclase 4