Once the signal binds to the receptor the receptor changes its shape or

Once the signal binds to the receptor the receptor

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Once the signal binds to the receptor, the receptor changes its shape or conformation. This conformation change might include the opening of an ion channel allowing ions to travel into the cell, or it might include changing the organization of domains like the extracellular domain of a receptor tyrosine kinase, a receptor class to be discussed later (Figure 1B). A receptor conformation
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NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE Page 2 “Diabetes and Insulin Signaling” by Kristy J. Wilson change causes the associated signaling molecule(s) to transition from inactive to active (Figure 1C). The signaling molecule(s) can carry the message through many different mechanisms. These mechanisms will be covered in the section about signaling mechanisms. The activated signaling molecule then influences the effector(s) that cause the short-term or long-term cellular change (Figure 1D). A short-term change can be stimulating cellular movement or changing the activation state of an enzyme going from inactive to active or active to inactive. This happens for instance when activating an enzyme to increase sugar metabolism. Long-term cellular changes are generally the result of changes in DNA transcription. For example, a protein could be made to begin cellular replication by activating the cell cycle. Signaling Mechanisms One mechanism for multi-protein signal transduction is the protein kinase cascade like the one illustrated in Figure 2A. A protein kinase is an enzyme that uses ATP to add a phosphate group to serine, threonine, or tyrosine residues of proteins. The determination of where a kinase will phosphorylate another protein is based upon the amino acids at the site of phosphorylation surrounding the amino acid to be phoshorylated. The amino acid sequence creates a specific binding site for the kinase so one kinase can only phosphorylate very specific proteins at specific sites. The addition of phosphate groups to these amino acids can alter the behavior of these proteins by changing their enzymatic activity (turning on or off), changing their association with other proteins, or changing their localization in the cell. Each protein kinase may have multiple amino acids that can be phosphorylated. Each phosphorylation site can change the kinase’s activity. In a protein kinase cascade, a receptor activates a signaling molecule that in turn activates a protein kinase that activates another protein kinase. This forms a kinase cascade that activates the next kinase until the final signaling molecule is reached, causing a cellular response. Figure 1. Components of signaling pathway. The major components of a pathway are (A) the signal, (B) the receptor, (C) the signaling molecule(s), and finally (D) the cellular effect.
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NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE Page 3 “Diabetes and Insulin Signaling” by Kristy J. Wilson The sites phosphorylated by the previous kinase activate the next kinase, but another site of phosphorylation on the same kinase could turn it off. The activity of each kinase in the cascade can be regulated in this manner. One common mode
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