0 6 Nitric nitric JJ 7 23 oxide-stimulated oxide-stimulated JJ 24 31 guanine guanine NN 32 42 nucleotide nucleotide NN 43 51 exchange exchange NN 52 54 on on IN 55 61 p21ras p21ras NN 61 62 . . . 64 67 The the DT 68 81 protooncogene protooncogene NN 82 88 p21ras p21ras NN 88 89 , , , 90 91 a a DT 92 101 monomeric monomeric JJ 102 103 G G NNP 104 111 protein protein NN 112 118 family family NN 119 125 member member NN 125 126 , , , 127 132 plays play VBZ 133 134 a a DT 135 143 critical critical JJ 144 148 role role NN 149 151 in in IN 152 162 converting convert VBG 163 176 extracellular extracellular JJ 177 184 signals signal NNS 185 189 into into IN 190 203 intracellular intracellular JJ 204 215 biochemical biochemical JJ 216 222 events event NNS 222 223 . . . 224 228 Here here RB 228 229 , , , 230 232 we we PRP 233 239 report report VBP 240 244 that that IN 245 251 nitric nitric JJ 252 257 oxide oxide NN 258 259 ( ( ( 259 261 NO no NN 261 262 ) ) ) 263 272 activates activate VBZ 273 279 p21ras p21ras NN 280 282 in in IN 283 288 human human JJ 289 290 T t NN 291 296 cells cell NNS 297 299 as as IN 300 309 evidenced evidence VBN 310 312 by by IN 313 315 an an DT 316 324 increase increase NN 325 327 in in IN 328 337 GTP-bound gtp-bound JJ 338 344 p21ras p21ras NN 344 345 . . . 346 348 In in FW 349 354 vitro vitro FW 355 362 studies study NNS 363 368 using use VBG 369 373 pure pure JJ 374 385 recombinant recombinant JJ 386 392 p21ras p21ras NN 393 404 demonstrate demonstrate VBP 405 409 that that IN 410 413 the the DT 414 424 activation activation NN 425 427 is be VBZ 428 434 direct direct JJ 435 438 and and CC 439 449 reversible reversible JJ 449 450 . . . 451 459 Circular circular JJ 460 469 dichroism dichroism NN 470 478 analysis analysis NN 479 486 reveals reveal VBZ 487 491 that that IN 492 494 NO no NN 495 502 induces induce VBZ 503 504 a a DT 505 513 profound profound JJ 514 528 conformational conformational JJ 529 535 change change NN 536 538 in in IN 539 545 p21ras p21ras NN 546 548 in in IN 549 560 association association NN 561 565 with with IN 566 573 GDP/GTP GDP/GTP NNP 574 582 exchange exchange NN 582 583 . . . 584 587 The the DT 588 597 mechanism mechanism NN 598 600 of of IN 601 611 activation activation NN 612 614 is be VBZ 615 618 due due IN 619 621 to to TO 622 637 S-nitrosylation s-nitrosylation NN 638 640 of of IN 641 642 a a DT 643 651 critical critical JJ 652 660 cysteine cysteine NN 661 668 residue residue NN 669 674 which which WDT 675 685 stimulates stimulate VBZ 686 693 guanine guanine NN 694 704 nucleotide nucleotide NN 705 713 exchange exchange NN 713 714 . . . 715 726 Furthermore furthermore RB 726 727 , , , 728 730 we we PRP 731 742 demonstrate demonstrate VBP 743 747 that that IN 748 754 p21ras p21ras NN 755 757 is be VBZ 758 767 essential essential JJ 768 771 for for IN 772 782 NO-induced no-induced JJ 783 793 downstream downstream JJ 794 803 signaling signaling NN 803 804 , , , 805 809 such such JJ 810 812 as as IN 813 821 NF-kappa NF-kappa NNP 822 823 B B NNP 824 834 activation activation NN 834 835 , , , 836 839 and and CC 840 844 that that IN 845 855 endogenous endogenous JJ 856 858 NO no NN 859 862 can can MD 863 871 activate activate VB 872 878 p21ras p21ras NN 879 881 in in IN 882 885 the the DT 886 890 same same JJ 891 895 cell cell NN 895 896 . . . 897 902 These these DT 903 910 studies study NNS 911 919 identify identify VBP 920 926 p21ras p21ras NN 927 929 as as IN 930 931 a a DT 932 938 target target NN 939 941 of of IN 942 945 the the DT 946 950 same same JJ 951 955 cell cell NN 955 956 . . . 957 962 These these DT 963 970 studies study NNS 971 979 identify identify VBP 980 986 p21ras p21ras NN 987 989 as as IN 990 991 a a DT 992 998 target target NN 999 1001 of of IN 1002 1004 NO no NN 1005 1007 in in IN 1008 1009 T t NN 1010 1015 cells cell NNS 1016 1019 and and CC 1020 1027 suggest suggest VBP 1028 1032 that that IN 1033 1035 NO no NN 1036 1045 activates activate VBZ 1046 1052 p21ras p21ras NN 1053 1055 by by IN 1056 1058 an an DT 1059 1065 action action NN 1066 1071 which which WDT 1072 1078 mimics mimic VBZ 1079 1083 that that DT 1084 1086 of of IN 1087 1094 guanine guanine NN 1095 1105 nucleotide nucleotide NN 1106 1114 exchange exchange NN 1115 1122 factors factor NNS 1122 1123 . . .