Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Nov 7;92(23):10585–10589. doi: 10.1073/pnas.92.23.10585

Complexes of p21RAS with JUN N-terminal kinase and JUN proteins.

V Adler 1, M R Pincus 1, P W Brandt-Rauf 1, Z Ronai 1
PMCID: PMC40656  PMID: 7479845

Abstract

RAS gene-encoded p21 protein has been found to increase in vitro phosphorylation of JUN via its kinase, JUN N-terminal kinase (JNK). This effect is mediated by increased phosphorylation of JNK in the presence of wild-type and oncogenic (Val-12) p21 protein in a dose-dependent manner. Oncogenic p21 protein is more potent in mediating this effect than its normal counterpart. Both normal and oncogenic p21 proteins bind to purified JNK and to JNK that is present in cell extracts from transformed fibroblasts and melanoma cells. Oncogenic and normal p21 proteins have also been found to bind to bacterially expressed JUN protein. This binding is dose dependent, enhanced by the presence of GTP, and depends on the presence of the first 89 amino acids of JUN (the delta domain), as it does not occur with v-jun. While the ability of both normal and oncogenic p21 proteins to bind JNK is strongly inhibited by a p21 peptide corresponding to aa 96-110, and more weakly inhibited by the p21 peptide corresponding to aa 115-126, p21-JUN interaction is inhibited by peptides corresponding to aa 96-110 and, to a lesser degree, by peptides corresponding to aa 35-47. The results suggest that the p21 protein interacts specifically with both JNK and JUN proteins.

Full text

PDF
10585

Images in this article

10586Fig. 1
on p.10586
10587Fig. 2
on p.10587
10587Fig. 3
on p.10587
10588Fig. 4
on p.10588
10589Fig. 5
on p.10589

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adari H., Lowy D. R., Willumsen B. M., Der C. J., McCormick F. Guanosine triphosphatase activating protein (GAP) interacts with the p21 ras effector binding domain. Science. 1988 Apr 22;240(4851):518–521. doi: 10.1126/science.2833817. [DOI] [PubMed] [Google Scholar]
  2. Adler V., Franklin C. C., Kraft A. S. Phorbol esters stimulate the phosphorylation of c-Jun but not v-Jun: regulation by the N-terminal delta domain. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5341–5345. doi: 10.1073/pnas.89.12.5341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Adler V., Unlap T., Kraft A. S. A peptide encoding the c-Jun delta domain inhibits the activity of a c-jun amino-terminal protein kinase. J Biol Chem. 1994 Apr 15;269(15):11186–11191. [PubMed] [Google Scholar]
  4. Barbacid M. ras genes. Annu Rev Biochem. 1987;56:779–827. doi: 10.1146/annurev.bi.56.070187.004023. [DOI] [PubMed] [Google Scholar]
  5. Chardin P., Camonis J. H., Gale N. W., van Aelst L., Schlessinger J., Wigler M. H., Bar-Sagi D. Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2. Science. 1993 May 28;260(5112):1338–1343. doi: 10.1126/science.8493579. [DOI] [PubMed] [Google Scholar]
  6. Chung D. L., Joran A., Friedman F., Robinson R., Brandt-Rauf P. W., Weinstein I. B., Ronai Z., Baskin L., Dykes D. C., Murphy R. B. Evidence that oocyte maturation induced by an oncogenic ras-p21 protein and insulin is mediated by overlapping yet distinct mechanisms. Exp Cell Res. 1992 Dec;203(2):329–335. doi: 10.1016/0014-4827(92)90006-t. [DOI] [PubMed] [Google Scholar]
  7. Gupta S., Campbell D., Dérijard B., Davis R. J. Transcription factor ATF2 regulation by the JNK signal transduction pathway. Science. 1995 Jan 20;267(5196):389–393. doi: 10.1126/science.7824938. [DOI] [PubMed] [Google Scholar]
  8. Leevers S. J., Paterson H. F., Marshall C. J. Requirement for Ras in Raf activation is overcome by targeting Raf to the plasma membrane. Nature. 1994 Jun 2;369(6479):411–414. doi: 10.1038/369411a0. [DOI] [PubMed] [Google Scholar]
  9. Lin A., Minden A., Martinetto H., Claret F. X., Lange-Carter C., Mercurio F., Johnson G. L., Karin M. Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2. Science. 1995 Apr 14;268(5208):286–290. doi: 10.1126/science.7716521. [DOI] [PubMed] [Google Scholar]
  10. Liwo A., Gibson K. D., Scheraga H. A., Brandt-Rauf P. W., Monaco R., Pincus M. R. Comparison of the low energy conformations of an oncogenic and a non-oncogenic p21 protein, neither of which binds GTP or GDP. J Protein Chem. 1994 Feb;13(2):237–251. doi: 10.1007/BF01891982. [DOI] [PubMed] [Google Scholar]
  11. Miura K., Inoue Y., Nakamori H., Iwai S., Ohtsuka E., Ikehara M., Noguchi S., Nishimura S. Synthesis and expression of a synthetic gene for the activated human c-Ha-ras protein. Jpn J Cancer Res. 1986 Jan;77(1):45–51. [PubMed] [Google Scholar]
  12. Moodie S. A., Willumsen B. M., Weber M. J., Wolfman A. Complexes of Ras.GTP with Raf-1 and mitogen-activated protein kinase kinase. Science. 1993 Jun 11;260(5114):1658–1661. doi: 10.1126/science.8503013. [DOI] [PubMed] [Google Scholar]
  13. Rodriguez-Viciana P., Warne P. H., Dhand R., Vanhaesebroeck B., Gout I., Fry M. J., Waterfield M. D., Downward J. Phosphatidylinositol-3-OH kinase as a direct target of Ras. Nature. 1994 Aug 18;370(6490):527–532. doi: 10.1038/370527a0. [DOI] [PubMed] [Google Scholar]
  14. Smeal T., Binetruy B., Mercola D. A., Birrer M., Karin M. Oncogenic and transcriptional cooperation with Ha-Ras requires phosphorylation of c-Jun on serines 63 and 73. Nature. 1991 Dec 12;354(6353):494–496. doi: 10.1038/354494a0. [DOI] [PubMed] [Google Scholar]
  15. Westwick J. K., Cox A. D., Der C. J., Cobb M. H., Hibi M., Karin M., Brenner D. A. Oncogenic Ras activates c-Jun via a separate pathway from the activation of extracellular signal-regulated kinases. Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6030–6034. doi: 10.1073/pnas.91.13.6030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Willumsen B. M., Vass W. C., Velu T. J., Papageorge A. G., Schiller J. T., Lowy D. R. The bovine papillomavirus E5 oncogene can cooperate with ras: identification of p21 amino acids critical for transformation by c-rasH but not v-rasH. Mol Cell Biol. 1991 Dec;11(12):6026–6033. doi: 10.1128/mcb.11.12.6026. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES