Cell Signalling 1 (19) Flashcards
what type of organisms are entirely reliable on signals from their envr?
single celled organisms
multi cell organisms receive signals form other cells that signal for what?
cell division
differentiation
death
Autocrine signaling
bind to receptors on cells that secrete them
what type of signaling do T-cell lymphocytes practice? & what molecule is excreted?
autocrine signaling
interleukin-2, cytokine
paracrine signaling
bind receptors & stimulate nearby cells
endocrine signaling
occurs when cells secrete signaling molecules into the blood
long distance, goes throughout the body
what type of signaling molecules are hormones?
endocrine signaling
synaptic signaling
similar to paracrine signaling but the signal is passed through a synapse (space) b/w the transmitting cell & the receiving cell; occurs b/w a neuron & another cell (usually another neuron or muscle cell)
specialized paracrine signaling
signaling by cell contact
must have cells with adjacent PMs (direct conduction from one cell to another without passing through the ECF)
gap junctions are what kind of signaling?
signaling by cell contact
whats the difference b/w lipophilic & lipophobic signals?
Lipophilic –> cross the PM, receptors are intracellular
Steroid hormones
Lipophobic –> don’t cross PM, receptors are extracellular
Any PRO based signal
Signals are transduced & amplified
transduction
process by which a signal crosses the membrane or is transferred to other molecules
amplification
process by which the effect of a signal is multiplied/increased
what are 2 ways transduction occurs?
phosphorylation
GPROs
phosphorylation transduction & ex
ligand binds to receptor, PRO gets phosphorylated & receptor may be mediating it & triggering events inside the cell
RTK receptors
G PRO transduction
extracellular receptor binds ligand, once bound will trigger a G PRO & that will amplify a signal causing cell to respond accordingly
summary of transduction & amplification
receptor binds signaling molecule
receptor changes shape
Shape change enables the receptor to interact with intracellular PROs
2nd messenger molecules are produced to amplify the signal
various effects can occur from 1 ligand
what are 2nd messengers responsible for?
transduction
what are 3 reasons why amplification is important?
Initial signaling molecule (hormone) to be in limited concentrations & still be effective
One hormone to activate numerous enzymes (one kinase molecule can activate many other kinase molecules)
(so it has a large enough effect to cause an event)
Coordination of several pathways simultaneously as all are induced by a single signal
summary of steroid hormones producing an endocrine signal
steroids are made from cholesterol (small & fat soluble)
travel through blood via carrier PROs
enter cells via diffusion
steroid has a high affinity for receptors in the cytoplasm or nucleus
hormone receptor complex binds to DNA at the promoter region, upstream of genes
transcriptional enhancement occurs
(slow, long-term response)
what are some types of steroid hormones?
glucocorticoids (including cortisol)
estradiol
testosterone
progesterone
what are the steps in activating glucogenesis?
- Diffuses into cell
- Binds specific receptor (PRO)
- Receptor dimerizes
- Dimer enter nucleus
- Dimer binds to GRE response element (DNA) on the PEPCK promoter (& other genes)
- Increases transcription rate, enzyme amount & enzyme activity gluconeogenesis
what are the kinds of lipophobic hormones?
water soluble hormones
PROs
neurotransmitters
cell-cell contacts
when is signal transduction used?
lipophobic signaling molecules
what are the steps in the signaling pathway for lipophobic signals?
- Recognition of stimulus by cell-surface receptor (specific, sensitive)
- “Transfer” across the membrane doesn’t ship ligand, receptor changes shape b/c of ligand & can now interact with an effector
- Effector (ex: adenylyl cyclase) molecules or a series of molecules on the interior of the membrane or cytosol create the next message (cAMP or calcium ions); usually a series of intervening steps before ultimate response (activations/inactivations)
Can produce 2nd messengers - Cessation of the response when signal disappears (ex: cAMP phosphodiesterase)
what are the diff kinds of movements in the nematode?
normal = sinusoldial
mutant G PRO - hyperactivity, sidewinding & twisting
mutant G PRO - lethargy, slow & limited tracks
what is the structure of a G PRO coupled receptor?
7 transmembrane domains
alpha helices
how do G PRO coupled receptors work?
through heterotrimeric G PROs
Alpha, beta & gamma subunits
Alpha & gamma both are embedded in the membrane
Beta subunit is free to move elsewhere
Turn on effector molecule which makes the 2nd messenger
Ex: epinephrine & glucagon turn on adenylyl cyclase to make cAMP (2nd messenger)
Others (ex: acetylcholine) use phosphoinositol, DAG 2nd messengers
Others (ex: photoreceptors) use cyclic GMP
how are GPCRs involved in making 2nd messengers?
binding the ligand causing a conformational change allowing the G-PRO to interact with the effector that produces the 2nd messenger signal
GPCR steps
- Ligand binds to receptor, shape changes & alpha subunits binds to receptor PRO
- Activation of the G PRO: exchanges GDP for GTP (no hydrolysis)
- RELAY: alpha dissociates from beta & gamma & binds to effector
- Activated effector produces 2nd messenger
- Alpha subunit hydrolyzes GTP –> GDP & deactivates itself
- Alpha subunit with GDP binds with beta & gamma subunits (trimeric PRO)
- G PRO coupled receptor kinase (GRK/GPCRK) phosphorylates the receptor
- Arrestin binds to phosphorylated receptor preventing it from binding with G PROs
how do G PROs differ from one another?
alpha subunits
what subunit besides the alpha subunit can activate effectors?
beta-gamma complex
steps of the cholera toxin causing water loss
Toxin binds to the receptor
Toxin brought into the cell via endocytosis
Cholera toxin binds to the alpha subunit
alpha subunit binds to adenyl cyclase with the toxin & is active
adenyl cyclase produces cAMP
cAMP activates the chloride channel
Na+ & water follow chloride ions out of the cell
Steps in stopping the GPCR signal
G RPO hydrolyzes GTP, inactivating itself
Receptor is phosphorylated
Phosphorylated receptor binds arrestin
Arrestin binds to clathrin
Endocytosis of receptors occurs
