Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK

Audrey Minden, Anning Lin, Martin McMahon, Carol Lange-Carter, Benoit Dérijard, Roger J. Davis, Gary L. Johnson, Michael Karin

Research output: Contribution to journalArticlepeer-review

1038 Scopus citations


Growth factors activate mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinases (ERKs) and Jun kinases (JNKs). Although the signaling cascade from growth factor receptors to ERKs is relatively well understood, the pathway leading to JNK activation is more obscure. Activation of JNK by epidermal growth factor (EGF) or nerve growth factor (NGF) was dependent on H-Ras activation, whereas JNK activation by tumor necrosis factor α (TNF-α) was Ras-independent. Ras activates two protein kinases, Raf-1 and MEK (MAPK, or ERK, kinase) kinase (MEKK). Raf-1 contributes directly to ERK activation but not to JNK activation, whereas MEKK participated in JNK activation but caused ERK activation only after overexpression. These results demonstrate the existence of two distinct Ras-dependent MAPK cascades - one initiated by Raf-1 leading to ERK activation, and the other initiated by MEKK leading to JNK activation.

Original languageEnglish (US)
Pages (from-to)1719-1723
Number of pages5
Issue number5191
StatePublished - Dec 9 1994
Externally publishedYes


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