Crosstalk Between Mitogen-Activated Protein Kinase and Phosphoinositide-3 Kinase Signaling Pathways in Development and Disease

Chapter
Part of the Systems Biology book series (SYSTBIOL)

Abstract

In animals, myriad chemical signals flow between and within cells to maintain life’s balancing act. The “flow” of these signals, or signaling pathways, ultimately dictates how cells respond to changes in their environment, from local tissue injury to food scarcity. During embryogenesis, the same signaling pathways function to transduce extracellular cues that guide development. Two of the most ubiquitous and evolutionarily conserved cell signaling pathways are the mitogen-activated protein kinase (MAPK) and the phosphoinositide-3 kinase (PI3K) pathways. The two pathways are involved in a wide range of critical cellular functions, such as cell growth and differentiation. They are also linked together as a part of a complex signaling network that regulates embryonic development, and the disruption of this network can result in a variety of diseases like cancers. Consequently, better mechanistic understanding of the MAPK and PI3K pathways and the crosstalk between them will inform strategies for future therapy. In this chapter, we will discuss the role of the MAPK and PI3K pathways in animal development and neoplastic transformations, with a focus on the role of multiple layers of crosstalk that go on between the two pathways.

Keywords

Mitogen-activated protein kinase (MAPK) Phosphoinositide-3 kinase (PI3K) Ras Raf Grb2 MEK TSC AKT Growth factor Receptor tyrosine kinase (RTK) Signaling Crosstalk Cell growth Differentiation Artery/vein specification Zebrafish Cancer Tumorigenesis Therapeutic target 

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Medicine, Division of Cardiovascular MedicineVanderbilt University School of MedicineNashvilleUSA
  2. 2.Research MedicineVA TVHS, Vanderbilt UniversityNashvilleUSA

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