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28.4: Intracellular Signaling Affects Focal Adhesions
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Cell Biology

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Intracellular Signaling Affects Focal Adhesions
 
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28.4: Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.

Some integrin-mediated stimulation pathways induce cell proliferation and promote cell survival. The adhesions originate at the cell membrane, but the signals are transmitted throughout the cell by G-proteins and protein kinases in a cascade. For example, thrombin binding to G-protein coupled receptors triggers intracellular signaling to activate integrins in platelets. Activated integrins bind to RGD-peptide sequences on blood proteins, such as fibrinogen. As the fibrinogens start forming bridges, the focal adhesions cluster together, and the platelets aggregate.

Integrins can also directly bind signaling proteins and relay the signals into the cell. In the Ras/MAP kinase pathway, focal adhesion kinase (FAK), a cytoplasmic protein kinase, is the best-studied modes of integrin signaling.  Studies suggest that focal adhesions contain many tyrosine phosphorylation sites and thus contain tyrosine-phosphorylated proteins such as FAK. Integrins cluster at cell-matrix junctions, and the β subunit recruits FAK through adaptor proteins such as paxillin or talin bound to the α subunit. The FAK proteins cluster at the site and phosphorylate a specific tyrosine site on each other. This creates a phospho-tyrosine docking site for Src proteins belonging to the cytoplasmic tyrosine kinases family. The FAK additionally phosphorylates other tyrosine sites, thus establishing docking sites for various proteins involved in intracellular signaling.


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Intracellular Signaling Focal Adhesions Integrins Membrane Receptors Effectors Intracellular Response Cascades Cell Proliferation Cell Survival G-proteins Protein Kinases Thrombin Platelets RGD-peptide Sequences Blood Proteins Fibrinogen Ras/MAP Kinase Pathway Focal Adhesion Kinase (FAK) Tyrosine Phosphorylation Sites

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