Mutants of Rab3A analogous to oncogenic Ras mutants. Sensitivity to Rab3A-GTPase activating protein and Rab3A-guanine nucleotide releasing factor.

作者: W.H. Brondyk , C.J. McKiernan , E.S. Burstein , I.G. Macara

DOI: 10.1016/S0021-9258(18)98366-3

关键词:

摘要: Rab3A is a Ras-like GTPase that believed to function in regulated secretion. A activating protein (GAP) and guanine nucleotide releasing factor (GRF) specific for have recently been described. In this study we described the biochemical activities of mutants codons 31, 81, 135, 166, which correspond 12, 61, 116, 146 Ras. The results demonstrate simple extrapolations from properties Ras are not valid all small GTPases. S31V-Rab3A Q81L-Rab3A had reduced basal activity, but surprisingly were sensitive effects Rab3A-GAP insensitive Rab3A-GRF. wild-type bound nonhydrolyzable GTP analog similar affinities Rab3A-GAP. vivo, percent (46%) (43%) complexed was similar. These findings indicate Rab3A-GRF interact with residues different those previously GAPs GRFs. Both A166V-Rab3A N135I-Rab3A increased intrinsic dissociation rates GDP. However, rate > 100-fold higher than suggesting that, two, would more likely be preferentially GTP-bound state.

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