| First Author | Gerwins P | Year | 1997 |
| Journal | J Biol Chem | Volume | 272 |
| Issue | 13 | Pages | 8288-95 |
| PubMed ID | 9079650 | Mgi Jnum | J:39299 |
| Mgi Id | MGI:86682 | Doi | 10.1074/jbc.272.13.8288 |
| Citation | Gerwins P, et al. (1997) Cloning of a novel mitogen-activated protein kinase kinase kinase, MEKK4, that selectively regulates the c-Jun amino terminal kinase pathway. J Biol Chem 272(13):8288-95 |
| abstractText | Mitogen-activated protein kinases (MAPKs) are components of sequential kinase cascades that are activated in response to a variety of extracellular signals. Members of the MAPK family include the extracellular response kinases (ERKs or p42/44(MAPK)), the c-Jun amino-terminal kinases (JNKs), and the p38/Hog 1 protein kinases. MAPKs are phosphorylated and activated by MAPK kinases (MKKs or MEKs), which in turn are phosphorylated and activated by MKK/MEK kinases (Raf and MKKK/MEKKs). We have isolated two cDNAs encoding splice variants of a novel MEK kinase, MEKK4. The MEKK4 mRNA is widely expressed in mouse tissues and encodes for a protein of approximately 180 kDa. The MEKK4 carboxyl-terminal catalytic domain is approximately 55% homologous to the catalytic domains of MEKKs 1, 2, and 3. The amino-terminal region of MEKK4 has little sequence homology to the previously cloned MEKK proteins. MEKK4 specifically activates the JNK pathway but not ERKs or p38, distinguishing it from MEKKs 1, 2 and 3, which are capable of activating the ERK pathway. MEKK4 is localized in a perinuclear, vesicular compartment similar to the Golgi. MEKK4 binds to Cdc42 and Rac; kinase-inactive mutants of MEKK4 block Cdc42/Rac stimulation of the JNK pathway. MEKK4 has a putative pleckstrin homology domain and a proline-rich motif, suggesting specific regulatory functions different from those of the previously characterized MEKKs. |
