Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant transformation frequently involves aberrant signaling from receptor tyrosine kinases (RTKs). These receptors commonly activate Ras/Raf/MEK/MAPK signaling but when overactivated can also induce the JAK/STAT pathway, originally identified as the signaling cascade downstream of cytokine receptors. Inappropriate activation of STAT has been found in many human cancers. However, the contribution of the JAK/STAT pathway in RTK signaling remains unclear. We have investigated the requirement of the JAK/STAT pathway for signaling by wild-type and mutant forms of the RTK Torso (Tor) using a genetic approach in Drosophila. Our results indicate that the JAK/STAT pathway plays little or no role in signaling by wild-type Tor. In contrast, we find that STAT, encoded by marelle (mrl; DStat92E), is essential for the gain-of-function mutant Tor (Tor(GOF)) to activate ectopic gene expression. Our findings indicate that the Ras/Raf/MEK/MAPK signaling pathway is sufficient to mediate the normal functions of wild-type RTK, whereas the effects of gain-of-function mutant RTK additionally require STAT activation.
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PMID:Differential requirement for STAT by gain-of-function and wild-type receptor tyrosine kinase Torso in Drosophila. 1218 76

Malignant transformation of cells is frequently associated with an augmented production of hyaluronan and the subsequent formation of a hyaluronan-matrix. In v-Src-transformed cells, hyaluronan directly activate cell motility in a tumor-specific manner. Despite its importance, the mechanism by which v-Src activates hyaluronan production remains unclear. Here we report that multiple signaling pathways are required for the augmented production of hyaluronan. Either the expression of a dominant negative Ras or the treatment of cells with manumycin A, a Ras farnesyltransferase inhibitor, was able to suppress hyaluronan production. In contrast, expression of MEK1EE, a constitutive form of MEK1, activated both hyaluronan synthase expression and hyaluronan production. AG-490, a Jak-2 inhibitor, or LY294002, a PI3K inhibitor, similarly suppressed the augmented production of hyarulonan. Taken together, our results suggest the involvement of multiple signaling pathways, including Ras-dependent and independent ones, in augmented hyaluronan production by v-Src.
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PMID:Requirement of multiple signaling pathways for the augmented production of hyaluronan by v-Src. 1737 76