cell signaling Flashcards
Detectors are the receptors, generally on the outside of the cell or organelle responsible for
recognizing a given signal.
There are 6 major classes of detectors.
- voltage dependent ion channels
- ligand dependent ion channels
- G protein coupled receptors
- Enzyme linked receptors
- nuclear receptors
- metabolic sensing
voltage dependent ion channels,
like Na channels and Ca channels, that sense a given voltage to change conformation.
Ligand dependent ion channels,
like acetylcholine nicotinic receptor, recognize a specific molecule or set of molecules.
G-protein coupled receptors,
like the muscarinic acetylcholine receptor, recognize a ligand and interact with a G-protein.
Enzyme linked receptors,
like the serine/threonine kinases, have enzymatic activity associated with ligand binding.
nuclear receptors that
are often transcription factors and regulate gene expression directly, such as steroid hormones.
metabolic sensing,
which is not really a receptor mediated signaling pathway. However, metabolic changes can cause signal pathways within cells, as in glucose-induced depolarization of pancreatic beta cells.
Other tools of cell signaling include
second messenger, which are molecules that relay signals from a receptor to target molecules in the cell.
A few important second messengers are
- Ca2+
- diacylglycerol (DAG) in the membrane
- inositol triphosphate (IP3) in the cytoplasm
- cyclic adenonsine monophosphate (cAMP)
- cyclic guanosine monophosphate (cGMP)
- nitric oxide (NO) a gas capable of permeating other cells.
In addition to second messengers, other tools involved in signaling include:
- Protein modification (phosphorylation, acetylation, glycosylation and more)
- Protein-protein binding and protein targeting responsible for localizing proteins where they need
to function - GTP/GDP exchange used by G proteins and small GTPases
Nearly any step in the cell signaling cascade can become a site for ____. This action results in the ______
termination
stopping of the signaling cascade.
Extracellular signaling molecules:
can diffuse away from the cell, become inactive, or all be taken into the cell, preventing their ability to signal on the surface.
Receptors: can become
desensitized and fail to bind to present ligand, reduction of binding or downstream signaling by the receptor, and internalizing the receptor so it cannot respond to extracellular signals.
2nd Messengers:
can be pumped out of cells or into storage sites, prevented from functioning by cleavage of cAMP and cGMP to AMP and GMP respectively by phosphodiesterases.
Protein: phosphorylation or dephosphorylation by kinases and phosphatases to
inactivate the cascade mediated by the protein
Protein binding/Targeting:
protein degradation
Signal termination is often modulated by the
signaling that it is involved in, i.e. negative feedback loops, constitutively active terminators (that are never off, such as phosphodiesterases) and signal induced “terminators” such as phosphatases and GTPases.
Amplification occurs when
a molecule in a cascade activates more than one of the next molecule in the cascade.
Any system where there is a ration of
greater than one to one of receptors to effectors uses some sort of amplification.
Amplification can occur at the level of
channels and receptors, second messengers, transducers or effectors.
Nodes are
points in a signaling network that have multiple “input” molecular pathways and multiple “output” pathways.
Node examples
Ca is a second messenger in many pathways, but not all the pathways modulated by Ca are activated every time Ca is released.
Multifunctional enzymes can function to:
(lPKA and PKC) that are involved in catalytic reactions of more than one substrate.
The result of multifunctional enzymes is that
there can be extensive communication between pathways, resulting in “cross talk” or many signaling events resulting from a particular ligand binding.
