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MAPK Signaling Cascades

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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
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The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
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RAS-MAPK in ALK targeted therapy resistance.

Gorjan Hrustanovic1,2, Trever G Bivona1,2

  • 1a Department of Medicine ; University of California at San Francisco ; San Francisco , CA USA.

Cell Cycle (Georgetown, Tex.)
|December 15, 2015
PubMed
Summary

Resistance limits ALK targeted therapy. Targeting ALK and MEK pathways together improved responses and prevented resistance in ALK-positive lung cancer models, suggesting a new treatment strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

Keywords:
ALKMAPKMEKRASlung cancerpolytherapyresistance

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  • Anaplastic Lymphoma Kinase (ALK) targeted therapy is a key treatment for ALK gene rearrangement positive (ALK+) lung adenocarcinoma.
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