Allostery and proteolysis: two novel modes of regulating integrin function.
Integrins are involved in transmitting signals between the cytoplasm and the extracellular matrix. Importantly, the transfer of information is bi-directional: signals flow inside-out and outside-in. Here, I discuss two potential modes by which integrin function is likely to be regulated. It is hypothesized that the integrin cytoplasmic tails are proteolytic substrates, and that cleavage of the cytoplasmic domain regulates the ligand binding affinity of integrins. It is also hypothesized that the ligand binding site is allosterically regulated by separate divalent ion binding sites that independently control ligand association and dissociation rate. Both hypotheses are suggested by reports in the literature and can be tested experimentally.
Smith
J W
JW
Cancer Research Center, Burnham Institute, La Jolla, California, USA.
D003593:Cytoplasm / Q000378:metabolism; D016023:Integrins / Q000502:physiology*; D008024:Ligands; D010447:Peptide Hydrolases / Q000502:physiology; D015398:Signal Transduction
D016023:Integrins; D008024:Ligands; D010447:Peptide Hydrolases