Table 1.
Parameters relevant for modeling the RAS activation cycle, for wildtype (WT) RAS and 15 oncogenic RAS variants. Rate constants correspond to those in Fig. 1. Variables have units s-1 for first-order reactions and M-1s-1 for second-order reactions. Values are formatted for the RAS isoform for which the measurement was taken. Values for KRAS are in bold, values for HRAS are italic, and values for NRAS are underlineds
RAS Mutation | ka, GTP (1/M/s) | kd,GTP (1/s) | ka,GDP (1/M/s) | kd,GDP(1/s) | khyd (1/s) | |||||
---|---|---|---|---|---|---|---|---|---|---|
None (WT) | 2.05E-4 | [37] | 6.33E-5 | [48] | 1.47E-4 | [48] | ||||
1.00E-4 | [174] | 4.20E-4 | [174] | 3.40E-4 | [174] | |||||
2.00E-3 | [175] | 2.00E-3 | [175] | 6.80E-4 | [175] | |||||
1.40E8 | [174] | 9.00E-5 | [176] | 5.10E7 | [174] | 1.20E-4 | [176] | 2.10E-4 | [176] | |
2.20E6 | [173] | 2.50E-4 | [177] | 2.30E6 | [173] | 1.08E-4 | [177] | 3.49E-4 | [177] | |
2.33E-4 | [180] | 3.00E-5 | [38] | 9.30E-3 | [38] | |||||
2.17E-4 | [180] | 2.17E-4 | [180] | |||||||
1.60E-5 | [173] | |||||||||
0.013 | [181] | |||||||||
| ||||||||||
G12A | 200E-3 | [175] | 2.00E-3 | [175] | 1.30E-5 | [175] | ||||
9.00E-5 | [176] | 5.00E-5 | [176] | 5.00E-5 | [176] | |||||
| ||||||||||
G12C | 2.00E-3 | [175] | 2.00E-3 | [175] | 4.90E-4 | [175] | ||||
6.00E-5 | [176] | 2.20E-4 | [176] | 1.80E-4 | [176] | |||||
| ||||||||||
G12D | 5.00E-4 | [174] | 2.00E-4 | [174] | 1.50E-4 | [174] | ||||
2.00E-3 | [175] | 2.00E-3 | [175] | 1.90E-4 | [175] | |||||
4.80E8 | [174] | 9.50E-4 | [176] | 7.00E7 | [174] | 1.60E-4 | [176] | 1.40E-4 | [176] | |
7.54E6 | [30] | 1.25E-3 | [30] | 3.16E6 | [30] | 5.16E-5 | [30] | 1.40E-4 | [30] | |
6.00E-4 | [180] | 1.67E-4 | [180] | 9.33E-5 | [180] | |||||
| ||||||||||
G12E | 4.90E-4 | [176] | 1.50E-4 | [176] | 1.60E-4 | [176] | ||||
| ||||||||||
G12R | 2.00E-3 | [175] | 2.00E-3 | [175] | 1.80E-5 | [175] | ||||
6.17E-3 | [181] | |||||||||
| ||||||||||
G12S | 2.00E-5 | [176] | 4.80E-4 | [176] | 1.20E-4 | [176] | ||||
| ||||||||||
G12V | 8.00E-5 | [174] | 3.33E-5 | [48] | 1.48E-5 | [48] | ||||
5.80E8 | [174] | 2.00E-3 | [175] | 1.30E-4 | [174] | 4.00E-5 | [174] | |||
9.11E6 | [30] | 9.00E-5 | [176] | 1.16E8 | [174] | 2.00E-3 | [175] | 4.20E-5 | [175] | |
2.00E-4 | [30] | 5.23E6 | [30] | 2.00E-5 | [176] | 5.00E-6 | [176] | |||
2.00E-5 | [38] | 1.50E-3 | [38] | |||||||
3.35E-5 | [30] | 5.23E-5 | [30] | |||||||
3.83E-3 | [181] | |||||||||
| ||||||||||
G13C | 8.00E-05 | [176] | 2.50E-4 | [176] | 1.10E-4 | [176] | ||||
| ||||||||||
G13D | 0.018 | [175] | 9.45E-4 | [48] | 5.17E-5 | [48] | ||||
6.30E-04 | [176] | 0.027 | [175] | 9.60E-5 | [175] | |||||
1.60E-4 | [176] | 1.90E-4 | [176] | |||||||
| ||||||||||
G13S | 7.00E-5 | [176] | 3.60E-4 | [176] | 3.20E-4 | [176] | ||||
| ||||||||||
G13V | 1.20E-4 | [176] | 3.40E-4 | [176] | 2.00E-4 | [176] | ||||
| ||||||||||
Q61H | 2.00E-3 | [175] | 2.00E-3 | [175] | 1.30E-5 | [175] | ||||
1.53E-4 | [177] | 1.60E-4 | [177] | 3.05E-5 | [177] | |||||
0.012 | [181] | |||||||||
| ||||||||||
Q61K | 1.50E-4 | [177] | 1.52E-4 | [177] | 7.07E-4 | [177] | ||||
| ||||||||||
Q61L | 2.00E-3 | [175] | 1.50E-4 | [48] | 1.83E-6 | [48] | ||||
2.67E-4 | [177] | 2.00E-3 | [175] | 8.00E-6 | [175] | |||||
2.67E-4 | [177] | 7.58E-6 | [177] | |||||||
| ||||||||||
Q61P | 3.17E-4 | [177] | 1.13E-4 | [177] | 2.72E-5 | [177] | ||||
| ||||||||||
Q61R | 1.12E-4 | [177] | 1.23E-4 | [177] | 6.10E-6 | [177] | ||||
| ||||||||||
Q61W | 2.00E-4 | [177] | 1.08E-4 | [177] | 2.53E-5 | [177] | ||||
| ||||||||||
10G11 | 5.50E-4 | [180] | 1.18E-3 | [180] | 1.83E-5 | [180] |
GGEF is RASGRF1. SGEF is SOS1. RGAP is RASA1. NGAP is NF1. *calculated from Lenzen et al. [173] using nucleotide dissociation rate as kr = 3.9 s-1 = kd,GDP,GEF and Kd (Kd = Kd4), such that kf = ka,GTP,GEF = kr/Kd. **calculated from Lenzen et al. [173], kr = Kd3kf3 = (0.6e-3)(3.4e4), assuming the same dissociation rate of GEF from RAS-GTP and RAS-GDP.