Oncoprotein-mediated signalling cascade stimulates c-Jun activity by phosphorylation of serines 63 and 73.
In resting cells, c-Jun is phosphorylated on five sites. Three of these sites reside next to its DNA binding domain and negatively regulate DNA binding. In response to expression of oncogenic Ha-Ras, phosphorylation of these sites decreases, while phosphorylation of two other sites within c-Jun's activation domain is greatly enhanced. Phosphorylation of these residues, serines 63 and 73, stimulates the transactivation function of c-Jun and is required for oncogenic cooperation with Ha-Ras. We now show that the same changes in c-Jun phosphorylation are elicited by a variety of transforming oncoproteins with distinct biochemical activities. These oncoproteins, v-Sis, v-Src, Ha-Ras, and Raf-1, participate in a signal transduction pathway that leads to increased phosphorylation of serines 63 and 73 on c-Jun. While oncogenic Ha-Ras is a constitutive stimulator of c-Jun activity and phosphorylation, the normal c-Ha-Ras protein is a serum-dependent modulator of c-Jun's activity. c-Jun is therefore a downstream target for a phosphorylation cascade involved in cell proliferation and transformation.
Smeal
T
T
Department of Pharmacology, University of California, San Diego, School of Medicine, La Jolla 92093-0636.
Binetruy
B
B
Mercola
D
D
Grover-Bardwick
A
A
Heidecker
G
G
Rapp
U R
UR
Karin
M
M
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004591:Electrophoresis, Polyacrylamide Gel; D008715:Methionine / Q000378:metabolism; D051379:Mice; D009154:Mutation; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism; D020575:Oncogene Proteins v-sis; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism; D012694:Serine; D015398:Signal Transduction; D015533:Transcriptional Activation
D020575:Oncogene Proteins v-sis; D009856:Oncogene Proteins, Viral; D010710:Phosphates; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D015682:Retroviridae Proteins, Oncogenic; D012694:Serine; D008715:Methionine; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src); D019908:Proto-Oncogene Proteins c-raf; D015689:Oncogene Protein p21(ras)