Differences in patterns of activation of MAP kinases induced by oncogenic ras-p21 and insulin in oocytes.
Oncogenic ras (Val 12-containing)-p21 protein induces oocyte maturation by a pathway that is blocked by peptides from effector domains of ras-p21, i.e., residues 35-47 (that block Val 12-p21-activated raf) and 96-110 and 115-126, which do not affect the ability of insulin-activated cellular p21 to induce maturation. Oncogenic p21 binds directly to jun-N-terminal kinase (JNK), which is blocked by the p21 96-110 and 115-126 peptides. This finding predicts that oncogenic p21, but not insulin, induces maturation by early and sustained activation of JNK. We now directly confirm this prediction by showing that oncogenic p21 induces activating phosphorylation of JNK (JNK-P) and of ERK (MAP kinase) (MAPK-P), whose levels correlate with oocyte maturation. p21 peptides 35-47 and 96-110 block formation of JNK-P and MAPK-P, further confirming this correlation and suggesting, unexpectedly, that raf-MEK-MAPK and JNK-jun pathways strongly interact on the oncogenic p21 pathway. In contrast, insulin activates only low levels of JNK-P, and, surprisingly, we find that insulin induces only low levels of MAPK-P, indicating that insulin and activated normal p21 utilize MAP kinase-independent signal transduction pathways.
Ranginwale
M
M
Department of Pathology and Laboratory Medicine, New York Harbor VA Health Care System, 800 Poly Place, Brooklyn, New York 11209, USA.
Smith
S
S
Flom
J
J
Chie
L
L
Kanovsky
M
M
Chung
D
D
Friedman
F K
FK
Robinson
R C
RC
Brandt-Rauf
P W
PW
Yamaizumi
Z
Z
Michl
J
J
Pincus
M R
MR
D000818:Animals; D005260:Female; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D017434:Protein Structure, Tertiary / Q000502:physiology; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism* / Q000494:pharmacology; D012741:Sexual Maturation / Q000187:drug effects / Q000502:physiology*; D014982:Xenopus laevis
D007328:Insulin; D010446:Peptide Fragments; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D016283:Proto-Oncogene Proteins p21(ras)