Functional differences in the. beta gamma. complexes of transducin and the inhibitory guanine nucleotide regulatory protein

Journal Article · Tue Mar 10 04:00:00 EST 1987 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00379a041· OSTI ID:6411268

Cerione, R A; Gierschik, P; Staniszewski, C; Benovic, J L; Codina, J; Somers, R; Birnbaumer, L; Spiegel, A M; Lefkowitz, R J; Caron, M G

The authors have examined the mechanism of inhibition of adenylate cyclase using the purified ..cap alpha.. and ..beta gamma.. subunits of bovine brain inhibitory guanine nucleotide regulatory protein (N/sub i/) (i.e., ..cap alpha../sub i/ and ..beta gamma../sub N/) and bovine retinal transducin (..cap alpha../sub T/ and ..beta gamma../sub T/) in reconstituted phospholipid vesicle systems. The addition of ..beta gamma../sub N/ or ..beta gamma../sub T/ to lipid vesicles containing the pure stimulatory guanine nucleotide regulatory protein (N/sub s/) from human erythrocytes as well as a resolved preparation of the catalytic moiety (C) of bovine caudate adenylate cyclase results in significant inhibition of guanine nucleotide stimulated cyclase activity (80-90%). The inhibition by these ..beta gamma.. subunit complexes appears to fully account for the inhibitory effects observed with holo-N/sub i/ or holotransducin. A variety of structure-function comparison of the ..beta gamma../sub N/ and ..beta gamma../sub T/ complexes were performed in order to further probe the molecular mechanisms involved in the inhibitory pathway. Whereas the ..beta.. subunits of ..beta gamma../sub N/ and ..beta gamma../sub T/ appear to be very similar, if not identical, on the basis of comparisons of their gel electrophoretic mobility and immunological cross-reactivity, clear differences exist in the apparent structures of ..gamma../sub N/ and ..gamma../sub T/. The functional differences between the ..beta gamma.. subunits of brain N/sub i/ and retinal transducin may reflect the clear structural differences in their ..gamma.. subunits, thus suggesting a possible role for ..gamma.. in the inhibition of adenylate cyclase by N/sub i/. Overall, these results indicate that the ..beta gamma.. complexes, as well as the ..cap alpha.. subunits, may have an important role in imparting the functional specificity necessary for nucleotide regulatory protein mediated signal transduction.

• Research Organization: Duke Univ. Medical Center, Durham, NC
• OSTI ID: 6411268
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 26:5; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMALS
AROMATICS
ATP
AZAARENES
AZOLES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMISTRY
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
BRAIN
CATTLE
CENTRAL NERVOUS SYSTEM
CHEMISTRY
CYCLASES
DAYS LIVING RADIOISOTOPES
DOMESTIC ANIMALS
DOSE-RESPONSE RELATIONSHIPS
ELECTRON CAPTURE RADIOISOTOPES
ENZYME ACTIVITY
ENZYMES
ERYTHROCYTES
ESTERS
EVEN-ODD NUCLEI
GUANINE
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
INHIBITION
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
LIPIDS
LYASES
MAMMALS
MATERIALS
NERVOUS SYSTEM
NUCLEI
NUCLEOTIDES
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PHOSPHOLIPIDS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PROTEINS
PURINES
PYRROLES
RADIOASSAY
RADIOISOTOPES
RUMINANTS
SULFUR 35
SULFUR ISOTOPES
TRITIUM COMPOUNDS
VERTEBRATES