In: Biology
Describe the common features shared by GPCRs and RTKs in their signaling mechanisms, focusing on how they are able to amplify signals. Specifically, how is the signal from one binding event (i.e., the binding of one ligand molecule to an individual receptor) propagated and strengthened?
Describe one difference in how GPCRs and RTKs transform extracellular signals into intracellular responses.
G-protein coupled receptors are the transmembrane receptors present on the cell membrane, they are also called metabotropic receptors. They contain three subunits namely alpha, beta, and gamma. Binding of agonist or antagonist make changes to the alpha, beta and gamma trimmer that triggers intracellular changes. Intracellular changes are triggered by three types of secondary messengers namely cyclic AMP, inositol triphosphate, and calcium.
Alpha unit is bound to one GDP molecule, binding of an agonist at receptor site causes replacement of GDP with GTP, and dissociation of the alpha unit from the beta-gamma unit. This is followed by a series of reactions mediated through secondary messengers that result in effector activation, again GTP is replaced with GDP, alpha-beta-gamma trimer associates. They produce effects within minutes.
Eg: muscarinic acetylcholine receptors, adrenergic receptors act through GPCR's.
The three important secondary messengers are cAMP (cyclic adenosine monophosphate), IP3 (inositol 1,4,5-triphosphate) act through calcium ions, and DAG (diacylglycerol). The secondary messengers cause phosphorylation or dephosphorylation of the enzymes and thus, produces the cellular response.
Kinase linked receptors respond mainly to protein and enzyme mediators. A single transmembrane helix connects the extracellular binding domain to the intracellular domain. Eg: insulin, growth factors. Binding of the ligand with the receptor structure is followed by the receptor dimerization and subsequent phosphorylation.
Thus, both the GPCRs and RTKs (receptor tyrosine kinases) are the membrane receptors and involve the phosphorylation. But one RTK can active more than 10 separate transduction pathways, whereas the GPCR cannot. This ability of RTKs to stimulate more than one signaling transduction pathway plays a key role in the cell growth and cell reproduction. Abnormal RTKs are associated with the pathogenesis of cancer.