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21.8: Amplifying Signals via Enzymatic Cascade

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Cell Biology

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Amplifying Signals via Enzymatic Cascade

21.8: Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the transfer of phosphate groups to the proteins and are specific for different target proteins.

Signal termination is essential for regulating the enzymatic cascades, and aberrant signal termination is often seen in tumor cells. Inactivation of phosphorylated signaling proteins is carried out by protein phosphatases that dephosphorylate the proteins. Therefore, phosphatases are considered the key regulators of signal transduction pathways. For example, several tyrosine phosphatases are recruited to the membrane when a ligand binding to the receptor stimulates receptor phosphorylation. SHP-1, a tyrosine phosphatase with an SH2 domain, binds to phosphotyrosines on activated cytokine receptors. On activation by JAK2- dependent phosphorylation, SHP-1 dephosphorylates specific JAKs and STATs to turn off the JAK/STAT signaling pathway.

In the case of G protein signaling, G protein itself possesses a GTPase activity that hydrolyzes its bound GTP into GDP and turns off the cascade. β-adrenergic receptor kinase, together with β-arrestin, also turns off G protein signaling. The receptor phosphorylated by β-adrenergic receptor kinase binds to β-arrestin, blocking the receptor from interacting with G proteins. Lastly, phosphodiesterases cause a reduction in the levels of second messenger cAMP, terminating the signaling through G protein-coupled receptor.


Amplifying Signals Enzymatic Cascade Ligand Cell-surface Receptor Intracellular Domain Shape Change Enzyme Function Signal Transduction Pathways Signal Amplification Downstream Target Phosphorylation Kinases Protein Phosphatases Signal Termination Tumor Cells Tyrosine Phosphatases SH2 Domain JAK/STAT Signaling Pathway G Protein Signaling GTPase Activity

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