A family of cAMP-binding proteins that directly activate Rap1

Science

Volumn 282, Issue 5397, 1998, Pages 2275-2279

  Kawasaki, Hiroaki ^a   Springett, Gregory M ^a   Mochizuki, Naoki ^a   Toki, Shinichiro ^a   Nakaya, Mie ^a   Matsuda, Michiyuki ^a   Housman, David E ^a   Graybiel, Ann M ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIC AMP; CYCLIC AMP BINDING PROTEIN; CYCLIC AMP DEPENDENT PROTEIN KINASE; GUANINE NUCLEOTIDE EXCHANGE FACTOR;

AMINO ACID SEQUENCE; ANIMAL TISSUE; ARTICLE; CELL DIFFERENTIATION; CELL GROWTH; GENE EXPRESSION; HUMAN; HUMAN TISSUE; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DOMAIN; PROTEIN FAMILY; PROTEIN LOCALIZATION; SECOND MESSENGER; SIGNAL TRANSDUCTION; TISSUE DISTRIBUTION;

1-METHYL-3-ISOBUTYLXANTHINE; ADRENAL GLANDS; ADULT; AMINO ACID SEQUENCE; ANIMALS; BRAIN; CELL LINE; CYCLIC AMP; CYCLIC AMP-DEPENDENT PROTEIN KINASES; FETUS; FORSKOLIN; GENE EXPRESSION; GTP-BINDING PROTEINS; GUANINE NUCLEOTIDE EXCHANGE FACTORS; HUMANS; IN SITU HYBRIDIZATION; MOLECULAR SEQUENCE DATA; PHOSPHORYLATION; PROTEINS; RAP GTP-BINDING PROTEINS; RAS GUANINE NUCLEOTIDE EXCHANGE FACTORS; RATS; SECOND MESSENGER SYSTEMS; SEQUENCE DELETION; SIGNAL TRANSDUCTION;

ANIMALIA; EUKARYOTA; MAMMALIA;

EID: 0032545328     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.282.5397.2275     Document Type: Article

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60. Another invariant motif, FGE (indicated by black diamonds in Fig. 1E) (70), occurs 10 amino acids upstream of the PR(A/T)A motif. The FGE motif is thought to make contact with the cyclic nucleotide and to stabilize its binding to the pocket (11). In cAMP-GEFs, the negatively charged glutamate residue of this motif (arrow in Fig. 1E) is replaced by neutral glutamine in cAMP-GEFI and by positively charged lysine in cAMP-GEFII and in cel cAMP-GEF. A lysine substitution at this position in the human PKARIα subunit has diminished ability to bind cAMP [D. Øgreid, S. O. Doskeland, K. B. Gorman, R. A. Steinberg, J. Biol. Chem. 263, 17397 (1988).] Nevertheless, cAMP-GEFII, like cAMP-GEFI, binds specifically to cAMP-bound agarose beads in vitro [ H. Kawasaki et al., unpublished observations] and also induces cAMP-dependent activation of Rap1A (Fig. 2).
61. Another invariant motif, FGE (indicated by black diamonds in Fig. 1E) (70), occurs 10 amino acids upstream of the PR(A/T)A motif. The FGE motif is thought to make contact with the cyclic nucleotide and to stabilize its binding to the pocket (11). In cAMP-GEFs, the negatively charged glutamate residue of this motif (arrow in Fig. 1E) is replaced by neutral glutamine in cAMP-GEFI and by positively charged lysine in cAMP-GEFII and in cel cAMP-GEF. A lysine substitution at this position in the human PKARIα subunit has diminished ability to bind cAMP [D. Øgreid, S. O. Doskeland, K. B. Gorman, R. A. Steinberg, J. Biol. Chem. 263, 17397 (1988).] Nevertheless, cAMP-GEFII, like cAMP-GEFI, binds specifically to cAMP-bound agarose beads in vitro [ H. Kawasaki et al., unpublished observations] and also induces cAMP-dependent activation of Rap1A (Fig. 2).
62. The sequences reported in this paper have been deposited in the GenBank data base. Accession numbers are as follows: human cAMP-GEFI, U78168; rat cAMP-GEFI, U78167; human cAMP-GEFII, U78516; rat cAMP-GEFII, U78517.
63. Supported by the James and Pat Poitras Research Fund and the Grayce B. Kerr Fund and by grants from NIH (grants NICHD R01 HD28341, NCI P01 CA42063, NHLBI P01 HL41484, and NCHGR R01 HG00299) and the Japan Science and Technology Agency and Health Sciences Foundation. We thank H. F. Hall, G. Holm, and P. Harlan for help; S. Hattori, J. Miyazaki, and T. Gotoh for reagents; and J. Borrow, N. Hopkins, M. Krieger, J. Lees, and P. Sharp for their helpful comments.