Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.25 (MEKK1)
 1,856 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma membrane-enriched fractions were prepared from human embryonic retinal cells transformed with either adenovirus E1A and oncogenic ras DNA, or E1A and E1B DNA. Ras comprised 5-10% of the membrane protein from the E1A/ras transformed cells, whereas the membranes from E1A/E1B transformed cells did not overexpress Ras. The membranes from E1A/ras cells contained MAP kinase kinase kinase (MAPKKK) activity, even after washing in 0.5 M NaCl, whereas the membranes from E1A/E1B cells did not. Neither membrane fraction contained MAP kinase kinase or MAP kinase activity after washing with 0.5M NaCl. Immunoblotting experiments revealed about 10-fold more c-Raf in the membranes from E1A/ras cells than from E1A/E1B cells, and 50-60% of the MAPKKK activity in Triton X100-solubilised membranes from E1A/ras cells was immunoprecipitated with anti-Raf antibodies. A striking enrichment of c-Raf in the plasma membranes of E1A/ras cells was also demonstrated by immunocytochemistry, where it was co-localized with Ras. The MAPKKK activity in E1A/ras membranes was unaffected by incubation with protein phosphatases or by inclusion of protein phosphatase inhibitors during isolation, nor was it activated by GTP-Ras or inhibited by GDP-Ras. The results support the view that Ras and c-Raf interact with one another, but that neither c-Raf phosphorylation nor its interaction with GTP-Ras are alone sufficient for activation. The identification of MAPKKK activity in the membranes of ras-transformed cells may prove useful in elucidating the mechanism by which Raf is activated by Ras.
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PMID:Specific association of activated MAP kinase kinase kinase (Raf) with the plasma membranes of ras-transformed retinal cells. 841 21

Adenovirus E1B proteins (19,000-molecular-weight [19K] and 55K proteins) inhibit apoptosis and cooperate with adenovirus E1A to induce full oncogenic transformation of primary cells. The E1B 19K protein has previously been shown to be capable of activating transcription; however, the underlying mechanisms are unclear. Here, we show that adenovirus infection activates the c-Jun N-terminal kinase (JNK) and that the E1B gene products are necessary for adenovirus to activate JNK. In transfection assays, we show that the E1B 19K protein is sufficient to activate JNK and can strongly induce c-Jun-dependent transcription. Mapping studies show that the C-terminal portion of E1B 19K is necessary for induction of c-Jun-mediated transcription. Using dominant-negative mutants of several kinases upstream of JNK, we show that MEKK1 and MKK4, but not Ras, are involved in the induction of JNK activity by adenovirus infection. The same dominant-negative kinase mutants also block the ability of E1B 19K to induce c-Jun-mediated transcription. Taken together, these results suggest that E1B 19K may utilize the MEKK1-MKK4-JNK signaling pathway to activate c-Jun-dependent transcription and demonstrate a novel, kinase-activating activity of E1B 19K that may underlie its ability to regulate transcription.
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PMID:Adenovirus E1B 19,000-molecular-weight protein activates c-Jun N-terminal kinase and c-Jun-mediated transcription. 963 86