Stress-activated protein kinases bind directly to the delta domain of c-Jun in resting cells: implications for repression of c-Jun function.
The transactivating function of the c-Jun proto-oncogene component of the AP-1 transcription factor is acutely regulated by a wide variety of cellular signals via modulation of phosphorylation of two serines (63 and 73). The viral oncoprotein, v-Jun, while containing homologous serines, is not phosphorylated in cells. A novel family of stress-activated protein kinases (SAPKs), also termed Jun N-terminal domain kinases (JNKs), are responsible for mediating S63/73 phosphorylation in response to a variety of cellular stimuli including tumor necrosis factor-alpha, heat stress and u.v. light. The p54 alpha 1, alpha 2, p54 beta and p46 beta SAPKs are shown to bind directly to c-Jun but not to v-Jun, with an absolute requirement for c-Jun amino acids 31-47, a region deleted in v-Jun. Inactive SAPKs tightly bind c-Jun in resting cells and may be a manifestation of the 'delta' inhibitor, a previously described repressor of c-Jun function.
Dai
T
T
Division of Cell and Molecular Biology, Ontario Cancer Institute, Toronto, Canada.
Rubie
E
E
Franklin
C C
CC
Kraft
A
A
Gillespie
D A
DA
Avruch
J
J
Kyriakis
J M
JM
Woodgett
J R
JR
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D002460:Cell Line; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun; D012097:Repressor Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases