3 4 5 Cell Signaling Flashcards
gap jxn transmit ___ signals
electrical
gap jxn 1/ link and 2/ fxns include
1/ cytoplasm of two neighboring cells
2/ rapid txmission of APs, diffusion of metabolites ( eg ATP) and second messengers (eg Ca2+)
heart, brain cells
membrane bound signaling molecules
like gap jxns but farther apart
contact-dependent - cells next to ea other
signaling molecule bound to PM of one cell and interacts directly with receptor of adjacent target cell
immune cells
communication by chemical signals - main steps
*major form of xfer of info* multi-layered transduction process release of signal by signaling cell transfer of signal detection by receptor decoding of signal by target cell activation of effector molecule response
neurocrine signals
neurotransmitters
i.e. noradrenaline, acetylcholine
released from nerve terminals into synaptic cleft to communicate with other neurons or non-neurons
endocrine signals
hormones
i.e. adrenaline, insulin, steroids
made and released from endocrine cells
transported to blood to target organ/cell
paracrine signals
i.e. histamine
made and released from endocrine cells, travel very short distances to target organ/cell
autocrine signals
i.e. prostaglandins
signaling and target cell is the same (itself)
hydrophobic signals
i.e. steroid hormones
diffused through membrane
activate nuclear transcription pathways (genomic pathway) via intracellular receptors
initiation of GENE TRANSCRIPTION!
hydrophilic signals
i.e. most signals
cell impermeable
recognized by plasma membrane receptors
PM receptors have 2 main fxns
1/ detect incoming signal
2/ transmit signal to cell interior
binding of ligand to receptors is (4)
of high affinity
saturable
reversible
specific
ligand-gated (ionotropic) receptors
ion channels
fastest of all receptors
binding of the ligand opens the channel to ions due to a conformational change
combines receptor, transducer, and amplifier
e.g. nicotinic receptors, GABA receptors
ligand-gated receptor functions (2)
1/ alter membrane potential to regulate excitable cells
2/ alter intracellular Ca2+ concentrations
g protein coupled receptors (GPCRs)
receptors coupled to heteroTRIMERIC g proteins (GDP or GTP) that fxn as transducers
7 transmembrane receptors
examples of GPCRs (2)
muscarinic receptors
adrenergic receptors
GPCRs are inactive when
g protein attached to GDP
GPCRs are active when
g protein attached to GTP
receptor tyrosine kinases
enzyme is intrinsic to receptor
single membrane spanning receptors
extracellular area binds the signal, causes dimerization of receptors and phosphorylation of receptor by intrinsic tyrosine kinase activity
cytosolic area has enzyme activity that tranduces signal
signal transduction by GPCRs requires 3 membrane bound proteins
1/ receptor
2/ G protein
3/ amplifier
N terminus of the GPCR
ligand binding domain
C terminus of the GPCR
exposed to cytosol
GPCR stimuli (long list)
light odors tastes ions amino acids amines nucleotides nucleosides prostaglandins lipids peptides proteins
when a GPCR is activated, this happens
GDP-a is released in exchange for GTP
a subunit detaches from B-gamma and attaches to GTP
so you are left with GTP-a and B-gamma
these 2 components of a GPCR can generate second messenger dependent cellular responses
GTP-a
Beta-gamma
active GTP-a is deactivated by
hydrolysis of GTP via GTPase that is intrinsic to the a subunit
leads to GDP-a + B-gamma (trimer formation)
4 types of G proteins
Gs
Gi
G1
G12
Gs amplifier
adenylyl cyclases (AC) stimulation
Gs amplifier
adenylyl cyclases (AC)
stimulation
B1 and B2
Gi amplifier
adenylyl cyclases (AC)
inhibition
a2
Gq amplifier
PLC-B
stimulation
a1
acetylcholine has two types of receptors
nicotinic
muscarinic
acetylcholine ligand-gated receptor
nicotinic receptor
acetylcholine GPCR
muscarnic receptor
main second messengers (5)
cAMP cGMP IP3 DAG Ca2+
second messenger AC/cAMP pathway
AC = membrane bound
activation generates cAMP from ATP
activated by Gs-a (GTP bound)
inhibited by Gi-a or Go-a (GTP bound)
Gs - AC increased - ____ second messenger
cAMP increased
Gi - AC decreased - ____ second messenger
cAMP decreased
Gq - PLC-B increased - ____ second messenger
IP3, DAG
Gq - PLC-B increased - ____ second messenger
IP3/Ca2+, DAG
hydrolysis of PIP2 by PLC leads to
DAG and IP3
PLC-gamma is activated by
tyrosine phosphorylated receptor kinases
upon hydrolysis of PIP2, DAG stays in the membrane and IP3 diffuses to the endo/SR to release _____
Ca2+
via binding to IP3 receptors
main fxn of DAG (result of second messenger PIP2) is to
activate protein kinase C
Ca2+ “on” mechanisms consist of (2 things)
1/ Ca2+ entry across plasma membrane
2/ Ca2+ release from intracellular stores
Ca2+ entry across PM is carried out by (2 things)
voltage gated channels
ligand gated channels
Ca2+ release from intracellular stores is carried out by (2 things)
IP3 receptors
ryanodine receptors
activation of CG results in generation of second messenger _____
cGMP from GTP
guanylyl cyclases are associated with (2 things)
membrane/particulate GC
cytosol/soluble GC
physiological activator of particulate GC (guanylyl cyclase)
natriuretic peptides
physiological activator of soluble GC (guanylyl cyclase)
nitric oxide (NO)
RGS proteins
regulators of g-protein signaling
terminate g-protein signaling
RGS proteins
“regulators of g-protein signaling”
they terminate g-protein signaling
they are GTPase activating (GAP), promoting GTP hydrolysis
termination of cAMP/cGMP signaling is done by
PDEs (phosphodiesterases)
cAMP is turned into 5’AMP by
PDE4
PDE1
cGMP is turned into 5’GMP by
PDE5
PDE1
small G proteins
monomeric G proteins
i.e. Ras and Rho
small G proteins are activated by
GPT exchange factors (GEFs)
small G proteins are turned off by
GAPs: GTPase activating factors
___ phosphorylate proteins
kinases
____de-phosphorylate proteins
phosphatases
these three amino acids participate in protein phosphorylation
serine
threonine
tyrosine
cAMP-dependent protein kinase (PKA)
serine/threonine kinase
inactive as a tetramer (2 regulatory subunits, 2 catalytic subunits)
____ binds to regulatory units of PKA to activate it
cAMP (2 cAMP molecules per regulatory subunit, so 4 cAMP molecules total)
(5) serine/threonine kinases
PKA: cAMP dependent protein kinase
PKG: cGMP dependent protein kinase
PKC: protein kinase C
caMK: Ca2+/calmodulin dependent protein kinase
MAPK/ERK: mitogen-activated protein kinase/extracellular signal related kinase
MAPKs
growth factors activate them
activated by phosphorylation of an upstream kinase
leads to activation of transcription factors
amplification
receptor–> G protein –> second messenger –> kinase –> phosphorylation
receptor tyrosine kinase
growth factor receptor
monomer, gets activated by dimerization
phosphorylation of receptor tyrosine kinases provides docking sites for a number of proteins containing SH2 domain or PTB domain, including ___ and ____
Grb2
PLC-gamma
___ attaches to Grb2
Sos protein (a GEF, activator of small G protein Ras)
___ activates Ras
Sos
activation of PLC-gamma and hydrolysis of PIP2 leads to
second messengers IP3 and DAG
Activation of PI3 kinase results in formation of ___
PIP3
RTKs have 2 jobs
1/ receptor (tyrosine kinase activity)
2/ recruitment of other molecules
this hormone is also a receptor tyrosine kinase
insulin
insulin receptor activates the
PI3K pathway via IRS (Insulin Receptor Substrate)
insulin receptor consists of
2 extracellular a chains and 2 transmembrane B chains (with intrinsic tyrosine kinase activity) connected by disulfide bonds
tyrosine kinases include (2)
growth factor receptor
insulin receptor
____ or ____ reverse phosphorylation
serine/threonine phosphatases or tyrosine phosphatases