Where does signal transduction occur?
inside the cell
What is signal tranduction?
Process in which Extracellular signaling molecules bind to specific receptors in target cells to initiate a chain of events
External signals induce what major type of fast response?
Change in activity or function of enzymes or proteins in the cell
External signals induce what major type of slow response?
Change in the amounts of proteins by change in expression of genes
What is a long distance, long lasting type of signaling?
endocrine signaling
Signal -> bloodstream -> distant target cells
Freely diffusible signals
What type of signaling acts locally, affects cells nearby (not as freely diffusable), and short lived?
Paracrine signaling
e.g. neurotransmitters
What type of signaling is released to themselves or release to cells of the same type?
Autocrine signaling
Cells secrete signal that feeds back and binds to a receptor on its won surface
E.g growth factor in cancer cells
What type of signaling does the immune cell elicit?
Direct cell signaling
Ag-presenting cell to T cells
*also known as juxtacrine signaling
What does acetylcholine do to heart muscle cells?
relax them
What does acetylcholine do to skeletal muscle cells?
contract them
What does acetylcholine do to salivary gland cells?
Cause them to secrete saliva
What are signaling cascade components?
signals, receptors, effectors
What can make up a cell signaling ligand?
proteins, small peptides, amino acid derivatives, hydrophobic molecules, steroid hormones like estrogen.
What are the main categories of cell signaling molecules?
small lipophilic molecules: steroid hormones
water soluble molecules- growth factors
What are two types of signaling module receptors?
intracellular receptors and cell surface receptors.
What is a specific type of intracellular receptors?
steroid receptor
What type of molecules can diffuse across the cytoplamic membrane and bind to intracellular receptors?
small hydrophobic signaling molecules
What are most signaling molecules?
hydrophilic and require cell surface receptors
What are intracellular ligands and signals?
VART
WHat are three main types of cell signaling receptors in the plasma membrane?
gated ion, G protein coupled receptors, enzyme coupled receptors
Where are gated ion channels common?
nervous tissue
What is special about GCPR?
7 pass transmembrane proteins
What does enzyme coupled receptor class include?
receptor tyrosine kinases
What is one major class of surface receptors that mediate signals inside the cell?
GPCRs
What type of receptors affect olfaction, sight and taste?
GPCRs
What type of transmembrane receptors are targets of many drugs?
GPCRs
What three parts is the G protein coupled receptors composed of?
extracellular domain- binds to ligand
transmembrane domain- anchors receptors
cytoplasmic domain- associated with G protieins
What are heterotrimeric G proteins?
are guanine nucleotide-binding proteins that consist of three subunits designated αβ γ
What have no instrinsic catalytic activity and regulated target enzymes?]?
g protein coupled receptors
What is the GPCR activity cascade?
GPCR-----> Trimeric G protein----> effector enzyme, adenyl cyclase---> 2nd messenger, cAMP----> Targets of 2nd messenger----> Biological response
What is GEF?
guanidine exchange factor
What causes GTP to change to GDP?
hydrolysis
What is the common subunit upstream of cAMP production?
Gsalpha
What does cAMP activate?
cAMP- dependent protein kinase, PKA, 4 subunits
What can active PKA do?
phosphorylate other proteins
What are the 4 consequences of phosphorylation by PKA?
- form part of structure
- change enzymatic target
- change intracellular localization of target protein
- alterations in abundance of target proteins
What does cholera cause you to do what?
pump a lot of water into your gut… lots of diahrea
What does cholrea target?
toxin targets a G-protein
How does cholera modify G proteins?
by keeping the G alpha in the GTP active form indefinitely… lots of cAMP…. lots of PKA… Lots of secretion of water
Continually pumping water and Cl out of the cells
What is desensitization?
ability to turn off or reject the signal
can lead to cancer
potentiate
turn up
attenuate
turn down
What happens when hormone levels drop?
decreased adenylyl cyclase activity…. decreased cAMP…
What will remove cAMP/ cGMP?
phosphodiesterases
How do you sequester the receptors?
endosomes
How do you destroy receptors of the cell?
endosomes and lysososmes (proteases)
What are G protein receptor kinases?
phosphorylate the receptor such that another protein called arrestin will bind to the 3rd intracellular loop and prevents Galpha from interacting with the third loop
- causing desensitiation of signal
Phosphoplipase C cleaves PIP2 to produce what?
IP3 and DAG
IP3 and DAG triggers?
release of Ca from endoplasmic reticulum
What are the two types of secondary messangers
cAMP and Ca
What type of enzyme coupled receptors do growth factors use?
tyrosine kinases
What is the structure of tyrosine kinases?
single pass transmembrane domain
What happens when a protein binds to a tyrosine kinase?
dimerization and then autophopshorylation occurs causing a scaffolding effect.
What binds to the SH2 domain of Grb2?
RTK
What does SH3 domain of Grb2 bind to?
prolines and SOS
What is the first human oncogene?
Ras, plays crucial role in cell dividsion and a frequent mutation in cancer
How many steps are involved to get to changes in protein activity in gene expression?
3 steps
What is the MAP kinase pathway?
Grb2-Sos- RAS-RAF-Mek-Erk
What seperates JAK STAT from tyrosine kinases?
More direct route, not using scaffolding
Goes straight to transcription regulation; however, lacks regulation
What is the difference in serine threonine?
Uses serine threonine instead of tyronsine kinases… SMAD controls cell proliferation