One of the most important second messengers is Ca++. In general, Ca++ enters the cytosol through gated ion channels in the plasma membrane and/or the endoplasmic reticulum. The ion channels in the plasma membrane, for example, could be voltage-gated, ligand-gated or temperature-gated. Those in the endoplasmic reticulum typically are gated by IP3.
Once in the cytosol, the Ca++ typically binds to a small protein, calmodulin. Once four Ca++ bind to calmodulin, it activates specific proteins inside the cell, such are certain protein kinases.
(Skeletal and cardiac muscle have another Ca++ binding protein termed troponin. However, it is related structurally to calmodulin. Also, in muscle, the endoplasmic reticulum is called sarcoplasmic reticulum.)
Cyclic AMP is also an important second messenger. It forms, as shown, when the membrane enzyme adenylyl cyclase is activated (as indicated, by the alpha subunit of a G protein).
The cyclic AMP then goes on the activate specific proteins. Some ion channels, for example, are gated by cyclic AMP. But an especially important protein activated by cyclic AMP is protein kinase A, which goes on the phosphorylate certain cellular proteins. The scheme below shows how cyclic AMP activates protein kinase A.
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QUESTION: What is the substrate for adenylyl cyclase?
QUESTION: What does a protein kinase do? QUESTION: What is the source of the alpha subunit of a G protein in the above figure? QUESTION: List the subunits which comprise protein kinase A. |
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Inositol triphosphate (IP3) and diacylglycerol (DAG) are important second messengers. Their formation begins with the binding of an extracellular regulatory molecule to a membrane receptor that activates a trimeric G protein. The alpha subunit of this G protein then activates phospholipase C, which acts on a membrane phospholipid. (What other membrane phospholipase have we discussed this quarter?)
Acting on a membrane phospholipid, phospholipase C cleaves off IP3, which is a small polar molecule. Remaining in the membrane is the DAG, which consists of glycerol and two fatty acids
The IP3 diffuses to the endoplasmic reticulum, which stores Ca++. The IP3 binds to and opens a ligand gated ion channel that allows Ca++ to move out into the cytosol, where the Ca++ activates various cellular processes. This is discussed further under calmodulin page. (Note that in muscle, the Ca++ is stored in the sarcoplasmic reticulum.)
Meanwhile, the DAG in the membrane activates protein kinase C, which in turn activates proteins inside the cell by phosphorylation.
Thus the initial binding of the extracellular regulatory molecule to the membrane receptor turns on an integrated repertoire of cellular events.
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QUESTION: What enzyme cleaves IP3 from a larger molecule?
QUESTION: What is is the larger molecule that is the source of the IP3? QUESTION: What does DAG do? QUESTION: What does IP3 do? QUESTION: What do you suppose is the basic structure of the membrane receptor to which the extracellular regulatory molecule binds? |
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