Mitogenic and survival signals initiated by polypeptide growth factors in mammalian cells are processed by receptors localized on the plasma membrane surface. These transmembrane receptors have a protein tyrosine kinase (PTK) activity domain that is localized at the cytoplasmic region of the protein molecule. The interaction of the growth factor ligands with the receptors induces their dimerization and activation through autophosphorylation. The activated PTK then activates one or multiple cytosolic signaling cascades including several protein kinase families, such as phosphatidylinositol 3-kinase-AKT (PI3K-AKT), extracellular signal regulated kinases (ERK), c-Jun N-terminal kinase (JNK), and stressactivated kinase (SAPK)-1/p38 mitogen-activated protein kinase (p38 MAPK). These kinases relay the signals from the cell surface to the nucleus to activate nuclear transcriptional factors, such as activating protein-1 (AP-1), which consists of Jun/Fos heterodimers, nuclear factor-kappa B (NF-κB), and p53 tumor suppressor protein, resulting in altered gene expression patterns and cellular responses, such as cell cycle progression and suppression of cell death. In addition to the large polypeptide growth factors that bind surface receptors, small molecule hormone ligands can enter the cell and bind tissue specific receptors, such as the androgen receptor (AR) in the prostate and the estrogen receptor in the breast, to mediate specialized signaling in their target cells and organs.
|Original language||English (US)|
|Title of host publication||Dietary Modulation of Cell Signaling Pathways|
|Number of pages||42|
|State||Published - Jan 1 2008|
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)