White: Cell signaling 1&2 Flashcards
Adenylyl cyclase is an example of
An effector
SOS is a _____ that binds _____
GEF, which binds and phosphorylates Ras (Small GTPase)
MAP kinase cascade
MAP kinaseX3 (Raf) ----> MAP kinaseX2 (Mek) ----> MAP kinase (Erk)----> Nucleus----> Increased gene transcription----> Uncontrolled cell division (cancer)
Activated PKA can
Regulate proteins by addition of phosphate group
Phosphate group can form part of structure that other proteins recognize
Alter activation/inactivation of target proteins
Alter intracellular localization of proteins
Alter abundance of proteins
GRKs– G-protein receptor kinase function
Phosphorylate receptor such that another protein -arrestin- binds to the 3rd loop of the receptor and prevents G-alpha from interacting with 3rd loop
Result is that G protein and G-alpha-GDP does not get converted to G-alpha-GTP by receptor
G-protein subunits
Alpha, beta, gamma subunits
Phospholipase C does what
Cleaves membrane protein PIP2
Receptor destruction
Endosomes + lysosomes/proteases
Hfe mutation
If Hfe is mutated it cannot associate with Tfr2 so Hepcidin expression cannot be increased
If Hepcidin can not be increased, ferroportin receptors will not be internalized and excess iron will flow into blood
Grb2 has ______ domain that binds _____
SH3 domain of Grb binds to Prolines in SOS
When iron is high, Hepcidin….
Hepcidin expression increases which lowers amount of ferroportins
DMT1
Iron transporter - transports iron into intestinal cell
Effects of DAG
DAG, along with calcium, bind PKC which phosphorylates a variety of membrane and cytoplasmic substrates
PIP2 produces
DAG and IP3
JAK-STAT pathway
Receptors bind ligand (cytokines)
Receptors dimerize and bind JAK
JAKs phosphorylate eachother and receptor
Receptor binds and phosphorylates STATs
STATs dissociate, dimerize, and go to nucleus
STATs bind DNA and cause transcription
Hormone level drop
Decreased adenylyl cyclase activity - decreased cAMP - decreased PKA activity
Remove signaling molecule
Phosphodiesterases will remove cAMP
What effector is activated when GPCR (G-protein coupled receptor) binds Gaq or Gao
Phospholipase C
Hereditary hemochromastosis causes
Uncontrollable iron absorption
Effects of IP3
Triggers release of calcium from ER by binding to IP3 gated calcium channel
Calcium can act as second messenger
RTKs bind to
SH2 domain on adaptor proteins (Grb2)
2 major cell responses from external signals
Change in activity or function of enzymes/proteins in the cell- Fast
Change in amounts of proteins by change in gene expression- Slow
Ferroportin
Iron transporter- transports iron out of intestinal cell and into blood
Calcium function as second messenger
Binds/activates calmodulin
Calmodulin then activates other proteins such as CaM kinase II which can activate transcription factors
Hfe
Membrane protein that binds to Tfr1
When iron binds Tfr1, Hfe is activated and binds Tfr2
Tfr2 then works through Smad pathway to induce Hepcidin expression
Epinephrine induces
Activation of PKA
cAMP is an example of
A second messenger
Hepcidin
Regulator of iron homeostasis
Binds ferroportin and causes internalization/destruction
JAK-STAT is a
More direct route for impacting transcription
Nitric oxide signaling is an example of
Paracrine signaling
Serine-Threonine receptor pathway
More direct route to impact transcription
Receptor activated by phosphorylation
Receptor binds R-Smad and phosphorylates
R-Smad binds Co-Smad and they move into nucleus to effect transcription
Steps of G-protein signaling
Ligand binds receptor
Conformational change in receptor
Receptor binds G-protein
Receptor acts as GEF
G-alpha protein changes conformation-replaces GDP with GTP
G-alpha becomes active and binds effector molecule
Effector molecule is activated (i.e.-adenylyl cyclase activates and forms cAMP)
Ras binds _____ and initiates
Raf, initiates MAP kinase cascade
Types of receptors
Transmembrane and intracellular
Hydrophobic molecules can cross membrane and bind intracellular receptors
RTK Receptor tyrosine kinase description
Important role in signal transduction
Enzyme linked receptors
Used for response to growth factors
Autophosphorylates
cAMP activates, it takes how many molecules of cAMP
Protein kinase PKA
2 cAMP molecules required to activate
Intracellular receptors effect what when activated
Typically effect gene expression
Erythropoeitin and JAK-STAT
Erythropoeitin employs JAK-STAT to initiate signaling
Receptor sequestration
Endosomal invagination of area of membrane w/receptor
Densensitization
Ability to turn off or reject signal
Downstream effects of PKA in fight/flight response
Generate lots of ATP liver-break down glycogen to glucose liver-inhibit glycogen synthesis Cardiac muscle- increase contraction Adipose tissue- Hydrolysis of triglycerides to generate glucose
