21.7
Versterking van signalen via tweede boodschappers
Veel receptorbindende liganden zijn hydrofiel; ze passeren het celmembraan niet, maar binden zich aan receptoren op het celoppervlak. Hun boodschap mo…
Second messengers are low molecular weight non-protein molecules that relay signals to targets within the cell when ligands bind to receptors on the cell surface.
Second messengers include ions, such as calcium ions; cyclic nucleotides, such as cyclic AMP; and small molecules, such as phosphatidylinositol phosphate derivatives diacylglycerol or DAG and inositol trisphosphate or IP3.
Calcium ions are a widely occurring second messenger. The intracellular calcium concentration increases in response to specific signals and triggers diverse physiological functions. For example, in muscle cells, an increase in cytosolic calcium results in muscle contraction.
Different G-protein coupled receptor families activate enzymes that generate second messengers, including adenylyl cyclase which produces cyclic AMP and phospholipase C which produces DAG and IP3.
These second messengers can activate multiple downstream kinases, further amplifying the signal.
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Q1: What are second messengers and why are they necessary in cell signaling?
Second messengers are low molecular weight non-protein molecules that relay signals from cell surface receptors to targets within the cell. They are necessary because many ligands are hydrophilic and cannot cross the cell membrane, so their message must be relayed by second messengers present in the cytoplasm. Examples include calcium ions, cyclic AMP, and inositol trisphosphate.
Q2: How does the phosphoinositol pathway generate second messengers?
In the phosphoinositol pathway, G protein-coupled receptors activate phospholipase C, which hydrolyzes phosphatidylinositol biphosphate (PIP2) into two second messengers: diacylglycerol (DAG) and inositol triphosphate (IP3). DAG remains near the cell membrane and activates protein kinase C, while IP3 translocates to the endoplasmic reticulum to release calcium ions.
Q3: What is the role of cyclic AMP in the cAMP signaling pathway?
Cyclic AMP (cAMP) is produced by adenylyl cyclase when activated by G protein-coupled receptors. Multiple copies of cAMP are generated from ATP molecules, allowing signal amplification. cAMP can stimulate protein kinase A, open calcium ion channels, and activate the enzyme Exchange-protein activated by cAMP (Epac).
Q4: How do second messengers amplify cellular signals?
Second messengers amplify signals by activating multiple downstream kinases and enzymes. For example, a single activated receptor can trigger adenylyl cyclase to produce many cAMP molecules, and each cAMP molecule can activate protein kinase A, creating an amplifying signals via enzymatic cascade effect that magnifies the original signal.
Q5: What is the function of calcium ions as a second messenger?
Calcium ions are widely occurring second messengers that trigger diverse physiological functions when intracellular concentration increases in response to specific signals. In muscle cells, increased cytosolic calcium results in muscle contraction. Calcium can be released from the endoplasmic reticulum through IP3-activated channels or through other calcium ion channels.
Q6: How does PIP3 differ from other second messengers in growth factor signaling?
Phosphatidylinositol triphosphate (PIP3) is a second messenger derived from phosphorylation of PIP2 when growth factors bind receptor tyrosine kinases. Unlike other second messengers, PIP3 recruits Akt (protein kinase B) to the membrane, where it regulates cell survival pathways including proliferation, apoptosis, and migration.
Q7: What is cyclic GMP and how does it compare to cyclic AMP?
Cyclic GMP (cGMP) is synthesized from GTP when guanylyl cyclase is activated, similar to how cAMP is produced. As a second messenger, cGMP induces protein kinase G (PKG), which has overlapping functions with protein kinase A. However, PKG expression is restricted to vascular tissues, lungs, and the brain, limiting cGMP's physiological scope.