Signaling 1 Flashcards
How does a cell know if has received a message?
- Non covalent binding of a ligand to a receptor induces a conformational change in the receptor which then triggers changes in other molecules inside the cell
- Receptor conformational change results in either a change in activity (if the receptor is an enzyme) or a change in affinity (if receptor lacks enzymatic activity)
- Messages that can’t enter cells directly are bound by receptors at the surface and the information is passed on through internally generated second messengers, molecules inside the cell that carry the signal away from the receptor
Signal amplification
-Binding of a ligand to a receptor molecule often results in a large increase in the concentration of some intracellular second messenger molecule, which amplifies the signal.
Importance of amplification
- Fewer receptors and signaling molecules are needed to get the cell to respond
- The time needed to get a response is shorter
- Second messengers can spread throughout cell (and even to neighboring cells through gap junctions)
Concentration of a signaling molecule
- Depends on the rate of synthesis and the rate of degradation
- Often controlled by feedback loops that regulate how fast the signaling molecule is produced. The rate of removal of a signaling molecule is usually constant.
Cellular response to a signal depend upon:
- Signaling molecule concentration
- Number of available receptors
- Receptor affinity for the signaling molecule
- Expression of tissue or cell-type specific second messenger systems
Target cell adaptation
A cell may down regulate expression of a hormone receptor gene after hormone levels have been high for a prolonged time
Change in a cell’s responsiveness to a specific signal concentration
Methods of changing a cell’s responsiveness to a specific signal concentration
- Changing the number of available receptors
- Changing the affinity of the receptor for its ligand
- Changing the response sensitivity of a second messenger pathway to receptor activation
Threshold effect
Little or no response is seen until a certain ligand concentration is reached and a small change in concentration gives a large change in response (similar to an all or none response)
Short distance signaling
Autocrine- self signaling
Paracrine- neighbor signaling
Synaptic- through synapses
Low affinity receptors
Long distance signaling
Endocrine- carried through the bloodstream
Require high affinity receptors
Signaling molecules- Small, rapidly diffusible molecules
Ex: No and Co
- alter enzyme activity directly
- Very short half lives
- Ex: NO can tranduce a neuronal signal to smooth muscle cells in the wall of a blood vessel (nitroglycerin prevents heart attacks)
Signaling molecules- Hydrophobic molecules
Steroids, retinoids, thyroid hormones
- Usually carried by binding proteins in the blood
- Relatively long half lives
- Bind nuclear receptors
Signaling molecules- Hydrophobic eicosinoids
- Derived from phospholipids
- Prostaglandins, prostacyclins, leukotrienes, thromboxanes
- inflammatory response and blood clotting
- Bind surface receptors
- Short half lives
- Usually act as autocrine signals
Signaling molecules- Hydrophilic molecules
Peptides, nucleotide and amino acid derivatives
- cell surface receptors
- short half lives
- hormones, growth factors, neurotransmitters, glucagon, insulin, oxytocin, acetylcholine, histamine…
Signaling molecules- sensory signals
Light, sound, smells, tastes
-Cell surface receptors
