A molecular redox switch on p21(ras). Structural basis for the nitric oxide-p21(ras) interaction.
We have identified the site of molecular interaction between nitric oxide (NO) and p21(ras) responsible for initiation of signal transduction. We found that p21(ras) was singly S-nitrosylated and localized this modification to a fragment of p21(ras) containing Cys118. A mutant form of p21(ras), in which Cys118 was changed to a serine residue and termed p21(ras)C118S, was not S-nitrosylated. NO-related species stimulated guanine nucleotide exchange on wild-type p21(ras), resulting in an active form, but not on p21(ras)C118S. Furthermore, in contrast to parental Jurkat T cells, NO-related species did not stimulate mitogen-activated protein kinase activity in cells transfected with p21(ras)C118S. These data indicate that Cys118 is a critical site of redox regulation of p21(ras), and S-nitrosylation of this residue triggers guanine nucleotide exchange and downstream signaling.
Lander
H M
HM
Department of Biochemistry, Cornell University Medical College.
Hajjar
D P
DP
Hempstead
B L
BL
Mirza
U A
UA
Chait
B T
BT
Campbell
S
S
Quilliam
L A
LA
D000595:Amino Acid Sequence; D018076:DNA, Complementary; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000737:chemistry* / Q000378:metabolism; D015689:Oncogene Protein p21(ras) / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D015398:Signal Transduction; D014162:Transfection
D018076:DNA, Complementary; D009569:Nitric Oxide; D015689:Oncogene Protein p21(ras)