ELIZA cgi-bash version rev. 1.90
- Medical English LInking keywords finder for the PubMed Zipped Archive (ELIZA) -
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288503 occurrences (No.86 in the rank) during 5 years in the PubMed. [no cache]
500 found
387) Here, we show that the JMML-associated Cbl mutant in complex with the Src family kinase Lyn promotes Cbl's adapter function, leading to increased association to PI3K regulatory subunit p85 and Lyn-dependent AKT pro-survival signalling.
* Juvenile myelomonocytic leukaemia-associated mutation in Cbl promotes resistance to apoptosis via the Lyn-PI3K/AKT pathway.
- Juvenile myelomonocytic leukaemia (JMML) is an aggressive myeloproliferative neoplasm in children characterized by granulocyte macrophage colony-stimulating factor (GM-CSF) hypersensitivity and resistance to chemotherapy. We recently identified c-Cbl (henceforth referred to as Cbl) as a GM-CSF receptor (GMR) responsive protein that targets Src for ubiquitin-mediated destruction upon GM-CSF stimulation and showed that a loss of negative regulation of Src is pivotal in the hyperactivation of GMR signalling in JMML cells. However, the mechanism regulating the chemoresistant nature of JMML has remained largely unknown. Here, we show that the JMML-associated Cbl mutant in complex with the Src family kinase Lyn promotes Cbl's adapter function, leading to increased association to PI3K regulatory subunit p85 and Lyn-dependent AKT pro-survival signalling. Notably, molecular or pharmacologic inhibition of the Lyn-PI3K/AKT pathway, but not the Ras/mitogen-activated protein kinase signalling axis, markedly increased the sensitivity of the otherwise chemoresistant Cbl mutant-JMML cells to chemotherapeutic agents currently used in the treatment of JMML patients. These results support the potential translational benefit of combining modalities that inhibit Lyn-PI3K/AKT signalling with traditional antileukaemia agents in the management of JMML.
=>1.機能, 関数, 役割, 働き, 2.機能する, 作用する, 働く, 役目を果たす, 3.社交的会合, パーティー, 儀式
Overview of noun function
The noun function has 7 senses (first 3 from tagged texts)
1. (43) function, mathematical function, single-valued function, map, mapping -- ((mathematics) a
mathematical relation such that each element of a given set (the domain of the function) is
associated with an element of another set (the range of the function))
2. (24) function, purpose, role, use -- (what something is used for; "the function of an auger is to
bore holes"; "ballet is beautiful but what use is it?")
3. (7) function, office, part, role -- (the actions and activities assigned to or required or
expected of a person or group; "the function of a teacher"; "the government must do its part"; "play
its role")
4. function -- (a relation such that one thing is dependent on another; "height is a function of
age"; "price is a function of supply and demand")
5. function -- (a formal or official social gathering or ceremony; "it was a black-tie function")
6. affair, occasion, social occasion, function, social function -- (a vaguely specified social
event; "the party was quite an affair"; "an occasion arranged to honor the president"; "a seemingly
endless round of social functions")
7. routine, subroutine, subprogram, procedure, function -- (a set sequence of steps, part of larger
computer program)
Overview of verb function
The verb function has 3 senses (first 3 from tagged texts)
1. (9) function, work, operate, go, run -- (perform as expected when applied; "The washing machine
won't go unless it's plugged in"; "Does this old car still run well?"; "This old radio doesn't work
anymore")
2. (3) serve, function -- (serve a purpose, role, or function; "The tree stump serves as a table";
"The female students served as a control group"; "This table would serve very well"; "His freedom
served him well"; "The table functions as a desk")
3. (1) officiate, function -- (perform duties attached to a particular office or place or function;
"His wife officiated as his private secretary")
--- WordNet end ---