Chapter 16 Flashcards
what is signal transduction
converting a signal from one form to another
the two types of receptors
cell surface (extracellular)
-most common
intracellular
cell to cell communication involves ____ molecules and once it reaches its target it must bind to ____ proteins
involves signal molecules / bind to receptor proteins
cell surface receptors are _____ where intracellular receptors are ______
cell surface - transmembrane proteins
intracellular - inside target cell
extracellular signal molecules bind to __ receptors and are very __
specific receptors and are very diverse
what are the main types of intercellular signaling
- endocrine
- paracrine
- synaptic
- contact dependent
what is synaptic intercellular signaling (3)
-very specific interaction between pre- and post-synaptic cells
-long range signaling is done by neurons at synapses
-very rapid response
what are the signal molecules of synaptic signaling
neurotransmitters
what is endocrine intercellular signaling ? (2)
-long range signaling using hormones secreted into the ECF then bloodstream
-hormones travel thru bloodstream, diffuse into tissues and act only on target cells that carry the corresponding receptor
what are the signal molecules of endocrine signaling
hormones
what is paracrine intercellular signaling (2)
-paracrine act locally only on neighboring cells
-secreted signal molecules do not diffuse far from origin
what are the signal molecules of paracrine signaling
local mediators (paracrines)
what are autocrines
signal molecules that act on the same cell that secreted the mediator
what is contact dependent intercellular signaling (2)
-requires direct contact between cells
-important during development and immune responses
describe the signal for contact dependent signaling
signal is membrane-bound and remains attached to cell surface
compare nervous vs endocrine systems
nervous
-neurotransmitters
-direct, not as widespread
-fast and fleeting effects
-change of proteins activity
endocrine
-hormones
-slower, longer lasting response
-more widespread effects
-changes to gene expression
what happens to cells that lack signals
they undergo apoptosis
compare cell surface vs intracellular receptors
cell surface
-hydrophilic extracellular signal binds to R on surface
intracellular
-small, hydrophobic signal molecules diffuse across the plasma membrane to bind to R in cytoplasm or nucleus
intracellular receptors are in the ____ or _____ and many are part of the _____ _____ superfamily
cytosol or nucleus
-part of the nuclear receptor superfamily
cholesterol and thyroxine hormones are ____ and mean what
hydrophobic = lipophilic and thus diffuse across membranes
describe cortisol intracellular receptors
activated cortisol receptor complex travels to nucleus and acts as a transcription regulator / activating or inactivating transcription
describe nitric oxide in cell signaling
N.O binds to an intracellular receptor on smooth muscle of blood vessel wall, causing relaxation (vasodilation)
-nerves in blood vessel release Ach which binds to receptors on endothelial cells and causes activation of N.O synthesis (N.O formation)
-N.O is released from endothelium
-N.O diffuses to nearby target smooth muscle cells
-this diffusion activates the soluble enzyme guanylyl cyclase which catalyzes the formation of cyclic guanosine monophosphate (cGMP)
-cGMP triggers relaxation (increases blood flow)
what is an example of a diffusible signal molecule
nitric oxide
basic pathway of cell communication (3)
1-transmembrane receptor (extracellular signal to intracellular) then
#2-molecular relay race (series of signaling proteins relaying signal inside cell)
#3-signal acts on effector proteins causing a target cell response
what is an example of a second messenger
cAMP or Ca2+
what are the 1st and 2nd messengers and describe the 2nd
1st - extracellular signal molecules
2nd- small intracellular signaling molecules (mediators)
=distribute the signal / relay the signal / amplify the signal / can receive input from more than one pathway
2 important types of molecular switches and they both depend on what
-protein kinases and protein phosphatases
~serine-threonine kinases and tyrosine kinases
-GTP binding proteins
~G proteins and monomeric GTPases
=they both depend on the gain or loss of phosphate for activation or inactivation
describe signaling by phosphorylation
-kinase phosphorylates the signaling protein (adds P)
-phosphatase dephosphorylates (removes P)
=protein flips between ON (has P) and OFF (no P)
describe signaling by GTP-binding
G proteins (GTP-binding proteins)
~G-protein-GTP
~G-protein-GDP
=exchanges bound GDP for GTP
with GDP is off
with GTP is on
describe signaling by GTPases
-guanine exchange factor (GEF) exchanges the protein bound GDP for GTP which activates the protein
-GTPase Activating Protein (GAP) hydrolyzes the bound GTP to GDP which inactivates the protein
describe Delta
a type of contact dependent signal where the signal is attached to the signaling cell and directly contacts an adjacent cell
what are the 3 classes of cell surface receptors
-ion channel coupled
-G-protein coupled
-enzyme coupled
which type of intercellular signaling travels via the bloodstream
endocrine
-hormones
describe ion channel coupled receptors
binding to ligand-gated ion channels opens them allowing ion flow
~ions act as intracellular molecules
what are GPCRs (3)
G-protein-coupled receptor = 7 pass transmembrane proteins
the mediator is…. a G-protein (trimeric GTP-binding protein) to relay signal in the cell interior
~largest family of cell surface receptors
describe G protein structure
=trimeric GTP-binding proteins
-attached to face of cytoplasm
-3 protein subunits (alpha, beta, gamma)
~alpha and gamma are tethered to membrane (lipid linked)
-2 conformations inactive (GDP) and active (GTP)
describe the activation of G-protein by GPCR
G-protein-GDP= inactive
-binding of extracellular signal to GPCR causes change in the receptor shape
-induces change of G-protein: GDP dissociates, GTP binds
-G-protein-GTP = active
~both alpha and beta/gamma are activated and can separate
-subunits can then cause effector activation
types of G proteins
-Gs Stimulatory G proteins
-Gi Inhibitory G proteins
-Gq stimulatory proteins
describe Gs Stimulatory G proteins
↑cAMP
=activate membrane bound enzyme adenylyl cyclase: converts ATP into cyclic AMP (cAMP)
describe Gi Inhibitory G proteins
↓cAMP
=inhibit adenylyl cyclase to decrease cAMP
=open K+ channels, inhibiting action potentials
describe Gq stimulatory proteins
↑Ca2+
=activate membrane bound phospholipase C which breaks apart inositol phospholipids to DAG and IP3
GPCR cAMP-dependent pathway steps (5)
- extracellular signal molecule activates GPCR, which activates Gs protein
- Gs alpha subunit activates adenylyl cyclase (AC) producing cyclic AMP (cAMP) from ATP
- cAMP attaches to inactive cyclic-AMP-dependent protein kinase (PKA) activating it
- PKA phosphorylates and activates another kinase - phosphorylase kinase will then activate other enzymes
- signaling cascade will continue until final target effector is activated to produce a cellular response
cAMP dependent transcription pathway steps (5)
- extracellular signal molecule activates GPCR which activates Gs protein
- Gs alpha subunit activates adenylyl cyclase producing cAMP
- cAMP then to PKA activating it
- active PKA moves to nucleus thru NPC and phosphorylate a transcription regulator activating it
- active TR binds to DNA regulatory sequence and either ↑ or ↓ transcription of target gene, altering gene expression
GPCR PIP2 pathway steps for IP3 (5)
- extracellular signal activates GPCR leading to conformation and activating Gq protein
- Gq beta/gamma subunit activates membrane bound enzyme phospholipase C (PLC)
- activated phospholipase C hydrolyzes membrane bound PIP2 into 2 intracellular messengers IP3 and DAG
- soluble IP3 diffuses to the ER and triggers opening of IP3 gated Ca2+ channels, releasing Ca2+ into cytosol
- Ca2+ then can bind to calmodulin activating it and bind to CaM-kinases (ca2+/calmodulin-dependent protein kinases) to activate other target proteins
GPCR PIP2 pathway steps for DAG (3)
- activated phospholipase C hydrolyzes PIP2 into IP3 and DAG
- DAG remains embedded in plasma membrane and along with Ca2+ activates membrane bound protein kinase C (PKC)
- PKC phosphorylates and activates intracellular proteins
what are enzyme coupled receptors and which do we cover
=transmembrane proteins
~single pass alpha helix with a ligand binding domain on ECF side and cytosolic catalytic domain
-cytosolic domain usually interacts with kinases
- RTKS (receptor tyrosine kinases)
describe activation of RTK steps (4)
- ligand binding causes dimerization which brings the kinase domains into contact , activating their cytosolic kinase domains
- kinase domains cross-phosphorylate one another on specific tyrosines
- each phospholated tyrosine (RTK) serves as a specific docking site for a different intracellular signaling protein
- intracellular proteins then relay the signal
RTK PIP2 pathway
activated signaling proteins on phosphorylated docking sites can then activate phospholipase C and complete normal PIP2 pathway
PIP2 -> DAG and IP3 -> Ca2+ -> PKC
RTK Ras MAPK pathway steps
- Ras GEF is activated via an adaptor docked on a P-tyrosine of RTK
- Ras-GEF activates Ras by converting it to Ras-GTP
- Ras-GTP initiates a phosphorylation cascade by activating 3 kinase signaling molecules
- MAP kinase kinase kinase (MAP3K) phosphorylates MAP kinase kinase (MAP2K) which phosphorylates MAP kinase (MAPK) that will finally phosphorylate effector proteins
what is MAPK
mitogen-activated protein kinase
give an example of MAP3K, MAP2K and MAPK
MAP3K = Raf
MAP2K = MEK
MAPK = MAPK
what does the RTK Ras MAPK pathway do
leads to increase in cell growth, cell division/ proliferation and cell cycle regulation
RTK PI3K-Akt signaling pathway steps (3)
- activated RTK activates PI3-kinase
- PI-3K phosphorylates a membrane inositol phospholipid = docking site for AKt also called protein kinase B
- PK1 and PK2 phosphorylate Akt activating and releasing it from the membrane
what does Akt do? and what happens if there’s none
Akt = promotes growth and SURVIVAL
no Akt - apoptosis occurs
describe Ras
most RTKs activate monomeric GTPase Ras
Ras = membrane bound GTP-binding protein with two conformations Ras-GDP or Ras-GTP
Ras is activated by Ras-GEF, converting it from Ras-GDP to Ras-GTP
*Ras-GEF is activated via an docked adapted
docked adaptor->activated Ras-GEF->activated activated Ras (Ras-GTP)
