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| MUTANT ALPHA-SUBUNITS OF GI2 INHIBIT CYCLIC-AMP ACCUMULATION |
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| Author(s): WONG YH, FEDERMAN A, PACE AM, ZACHARY I, EVANS T, POUYSSEGUR J, BOURNE HR |
| Source: NATURE Volume: 351 Issue: 6321 Pages: 63-65 Published: MAY 2 1991 |
| Times Cited: 222 References: 30 |
| Abstract: ONE or more of three G(i) proteins, G(i1-3), mediates hormonal inhibition of adenylyl cyclase 1-3. Whether this inhibition is mediated by the alpha or by the beta-gamma-subunits of G(i) proteins is unclear 1,2. Mutations inhibiting the intrinsic GTPase activity of another G protein, the stimulatory regulator of adenylyl cyclase (G(s)), constitutively activate it by replacing either of two conserved amino acids in its alpha-subunit (alpha-s) 4-7. These mutations create the gsp oncogene which is found in human pituitary and thyroid tumours 5,8. In a second group of human endocrine tumours, somatic mutations in the alpha-subunit of G(i2) replace a residue cognate to one of those affected by gsp mutations 8. This implies that the mutations convert the alpha-i2 gene into a dominantly acting oncogene, called gip2 (ref. 8), and that the mutant alpha-i2 subunits are constitutively active. We have therefore assessed cyclic AMP accumulation in cultured cells which stably or transiently express exogenous wild-type alpha-i2 complementary DNA or either of two mutant alpha-i2 cDNAs. The results show that putatively oncogenic mutations in alpha-i2 constitutively activate the protein's ability to inhibit cAMP accumulation. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV CALIF SAN FRANCISCO, DEPT PHARMACOL, SAN FRANCISCO, CA 94143 USA
2. GENENTECH INC, S SAN FRANCISCO, CA 94080 USA
3. UNIV CALIF SAN FRANCISCO, DEPT MED, SAN FRANCISCO, CA 94143 USA
4. UNIV CALIF SAN FRANCISCO, CARDIOVASC RES INST, SAN FRANCISCO, CA 94143 USA
5. UNIV NICE, FAC SCI, CNRS, CTR BIOCHIM, F-06034 NICE, FRANCE |
| Publisher: MACMILLAN MAGAZINES LTD, 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: FK193 |
| ISSN: 0028-0836 |
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