Basic sequence of signaling
A Signal Transduction Pathway is a sequence of molecular events and chemical reactions that lead to a cell's response. It involves: a signal, a receptor, and a response.
1. Signals are released from other tissues
2. A signal molecule binds to a receptor protein in the cell surface or inside the cytoplasm.
3. Signal binding changes the three-dimensional shape of the receptor and expose its active sites
4. The activated receptor activates a signal transduction pathway to bring about cellular changes.
a. Short-term changes: enzyme activation, cell movement
b. Long-term change: altered DNA transcription.
Recap: Signal > Receptors > Transducer > Cellular Response. Signal binds to Receptors and transducer pass on the information to trigger cellular response.
Three important characteristics for Signaling
1. Signal has to be amplified for drastic response 2. physical separation of signal perception and response: distribute signal to different targets. 3. Specificity: same signal might be different in responses, so the receptor must be very precise and link signal perception to other molecule downstream.
4 Types of receptors
There are 4 receptor mechanisms found in signal transduction pathways of eukaryotic cell: 3 membrane-bound and 1 cytoplasmic receptors. The 3 membrane-bound receptors are: ligand-gated ion channel, protein kinase receptor, and G protein-coupled receptor
Cytoplasmic steroid receptor mechanism
Cytosol is the signal perception in cytoplasm. Cytosol is a composed of a receptor protein and a chaperone protein. Cytosol is so big that it cannot enter into the nucleus. However, when the hormone from blood stream travels into cytoplasm and bind with the receptor on cytosol, the receptor structure changes and result in dissociation of chaperone protein. Therefore, the activated receptor now is small enough to enter into the nucleus and binds with the gene. This binding will triggers gene expression.
Acetylcholine receptor mechanism for Na+ ion (Ligand-gated ion channel)
When two molecules of acetylcholine bind with receptor, it triggers the opening of the ion gate. Na+, which is more concentrated outside the cell than inside, rush into the cell, moving in response to both concentration and electrical potential gradients. The change in Na+ concentration in the cell initiates a series of events that result in muscle contraction.
Protein Kinase Receptors
receptor proteins become protein kinases when they are activated by the signal. Two protein kinases can phosphorylate each other or activate each other, and become a dimer, thus changing their shape and therefore their function. This dimer can further phosphorylate other protein. When you see the term "kinase," it means that this enzyme utilize ATP (source of phosphate for phosphorylation).
Insulin Reception (Protein Kinase Receptor)
Insulin is a protein hormone with its receptor carrying enzyme activity. Insulin receptors originally have two subunits dissociated from each other. The binding of insulin and the receptors trigger the dimerization, and receptors become activated into protein kinase. The activated protein kinase can phosphorylate each other and further phosphorylate insulin response substrates, which then initiate many cellular responses including the insertion of glucose transporters into plasma membrane.
* "Protein kinase" converts protein into proteinP (P = Phosphate) by utilizing ATP. * "Phosphatase" can convert ProteinP into protein by taking away the P (ATP is released).
Beta-Adrenergic Receptor mechanism (G Protein-linked receptor)
This receptor is specifically designed for epinephrine. The receptor used to be associated with the heterotrimeric G protein. When epinephrine binds to the receptor, GDP of the G Protein is converted into GTP which causes the conformation change in the G protein. The GTP-bound subunit then separates from the rest of the protein, diffusing in the plane of the phospholipid bilayer until it encounters and activate an enzyme called adenylyl cyclase. Once adenylyl cylcase is activated, it converts ATP to cAMP. cAMP will then trigger a lot of things downstream. In this case, cAMP is a secondary messenger.
It has three subunits: alpha, beta, and gamma subunits. The alpha subunit binds to GDP. G proteins can bind to three different molecules: the receptor, GDP>P, and an effector protein.
G Cycle or On/Off State of G-protein
Let starts with the 'off' position. It has three subunit at off position: alpha, beta, and gamma. Activated G protein-linked receptor will activate G protein, resulting in conversion of GDP into GTP and dissociation of beta&gamma subunits of the protein. And the single alpha subunit of protein is now at 'on' position. From 'on' to 'off' state, we need to hydrolyze GTP (take away phosphate) into GDP and bind alpha subunit with Beta-gamma complex.