LMD Lecture Flashcards
six steps of cell-cell communications
synthesis, release, transport, detection, change, removal
Large distance extracellular signalling is mediated by
hormones
Short distance extracellular signalling is mediated by
neurotransmitters and some growth factors
Autocrine signalling mediated by
growth factors
Autocrine signalling generally act on themselves to ____
regulate proliferation
Growth factors have which modes of communication?
All three
Epinephrine have which modes of communication?
Endocrine and Paracrine
4 types of intracellular signalling
Contact dependent, paracrine, synaptic, endocrine
3 types of signalling according to distance
endocrine, paracrine, autocrine
How was cell communication discovered?
Protrusion of yeast cells
Difference between synaptic and endocrine
(1) One neurotransmitter - many actions, hormones require specificity, (2) endocrine - bloodstream, synaptic - neural transmission, (3) endocrine - operates over a longer period of time, synaptic - immediate response to signal
- the endocrine system secretes hormones into the bloodstream and the nervous system secretes neurotransmitters which are released directly onto their target cells.
- the nervous system responds faster than the endocrine system.
- the nervous system typically activates its targets quickly and only for as long as action potentials are sent to the target. The endocrine system tends to have longer-lasting effects.
Lipid soluble hormones
Steroids, thyroid hormones, retinoids
Steroids are from
lipids derived from cholesterol in SER
What provides uniqueness for steroids
different fxnal groups around core structure
Steroids turn on what…
GENES!
Function of thyroid hormones
help set basal metbaolic rate, activate enzymes involved in catabolism of fats and glucose
Vitamin A derivatives and their functions
Retinoids, effects on proliferation & differentiation plus cellular death
Water soluble hormones
amino acid derivatives and eicosanoids
Modified AA hormones
serotonin, melatonin, histamine, epinephrine
Large peptide hormones
insulin and glucagon
Eicosanoids are derived from
arachidonic acid
Examples of eicosanoids
prostaglandins and leukotrienes
Action of prostaglandins
ACT ON CELL SURFACE RECEPTORS DESPITE BEING LIPOPHILIC
How do water soluble hormones act?
Bind to cell surface receptors –> second messenger system
Narrate mechanism of vessel dilation
Neuron secretes neurotransmitter, Ach binds to Ach receptor in endothelial cell producing NO which increases GMP leading to vessel dilation
NO’s mode of cell communication
PARACRINE
T/F. NO is stable.
F
T/F. NO has local effects and is NOT systemic
T
8 examples of neurotransmitters
Acetylcholine, glycine, glutamate, GABA, dopamine, serotonin, epienephrine, histamine
How do neurotransmitters work/
They bind on cell surface receptors that induce conformation chane on ion channels causing ion influx
Activators of NMDA receptor
Glycine glutamate
Antagonist of NMDA receptor
Homocysteine, TCF
3 classes of cell surface receptors
GPCR, ion channel, enzyme coupled
Examples of GPCR
epinephrine, glucagon, serotonin
GPCR is involved in
light detection (eye), odorant detection (nose), detection of certain hormones and neurotransmitters
Two types of G proteins
Gs and Gi (stimulates, inhibits)
Example of ion channel receptor
Ach receptor
Where are ion channel receptors
Neuronal plasma membrane, plasma membrane of muscle cells
Functions of ion channel
saltatory conduction, muscle contraction
Cytokines and interferons are what type of receptors
Tyrosine kinase linked receptors
Examples of non catalytic receptors that are coupled to tyrosine kinases
Erythropoietin, inteferon
Binding of a ligand on Tyr kinase-linked receptor results into
Dimer formation then activation of tyrosine kinases
Difference between RTKS and Tyr kinase linked receptors
RTKs have intrinsic catalytica ctivity
What binds to RTKs
Growth factors - peptide/protein hormones such as NGF, PDGF, insulin
What AA residues are phosphorylated by RTKs?
serine, threonine
A and B must be present to activate Y., What’s Y?
Integrator protein
Another name for Y if A and B must be present to activate Y
Coincidence detector
Enhances speed, efficiency and specificity of response
Scaffold protein
Site at which GTP binds on G protein
ALPHA SUBUNIT
What is activated by Gs alpha subunit
Adenylyl cyclase
Second messengers
cAMP, IP3, DAG, Calcium
What receptor of a signal pathway is not being participated by cAMP
RTK
function of cAMP
activate PKA
Regulates cAMP to shut off the signal
phosphodiesterase. pyrophosphate becomes driver for cAMP synthesis
Effects of PKA activation
on adipocytes: stimualte production of FA, on ovarian cells: increase estrogen
PKA phosphorylates glycogen phosphorylase causing activation. T/F
True
PKA phosphorylates glycogen synthase causing activation. T/F.
False
Low cAMP levels trigger GPCR to produce PKA.
False. Epinephrine triggers GPCR increasing cAMP, and PKA in the process. Epinephrine is a stress hormone and the activation of PKA leads to glucose utilization activating glycogen phosphorylase and inhibiting glycogen synthase.
GPCR acts to 2 enzymes relevant in our discussions
adenylyl cyclase and phospholipase C-Beta
GPCR A subunit —> ??? —> ____ + _____ –> Calcium release
??? is phopholipase C B, IP3 and DAG
DAG acts on
Protein Kinase C
IP3 acts on
ER to release calcium
Effects of calcium
Exocytosis of insulin, muscle contraction, Ca-calmodulin affecting gene expression
MAP kinase pathways are activated by
RTKs
MAP kinase pathway: ___ –> ____ —> MAP Kinases
Ras GTPase —> rac —> MAP kinase
MAPK activation leads
translocation into nucleus and phosphorylate proteins
Central driver of MAP kinase paths
cdc42/rac
Stress reponse and apoptosis
rac-MEKKs-MEK 3/6-p38MAPK->MAPKAP2 or ATF and elk. MAPKAP2 leads to hsp27
Stress response and proliferation
rac-MEKKs-JNKK1/2-JNK1/2-ATF,jun,elk
Proliferation and differentiation
rac-ras-raf-MEK-ERK-elk,RSK,fos
Complete: ras-__-___-___-___ or _____
ras-raf/MAPKKK-mek/MAPKK-erk/MAPK–change in protein activity or change in gene expression
Negative regulator of water soluble hormones
phosphodiesterase
Parts of a nuclear receptor
transcription activating domain, ligand binding domain, DNA binding domain
Inhibitory proteins bind to the C-terminal portion of an inactive protein in the nuclear receptor superfamily. T/F
T
Nuclear hormone receptor binds to DNA has heterodimers. T/F.
F either hetero or homo
What stabilizes ligand in a nuclear receptor protein?
Alpha helix in C terminal portion.
Binds to transcription activating domain to allow DNA binding element to bind successfully.
Coactivator proteins
___ activates ___ leading to ___. Example is estrogen.
Steroids or the nuclear receptor superfamily of proteins activate early primary response genes leading to activation of delayed secondary response genes.
Narrate gene activation pathway
1o transduction - relay - transduce and amplify - integrate - spread - anchor - modulate - effector protein activation
Cell death receptors belong to ___ family
TNF family
Classic cell death receptor
Fas
Ultimate effectors of apoptosis and the reason for their name
Caspases. Have Cys in active site and cleave after Asp
Regulators of apoptosis
Bcl2 family
Intrinsic pathway of apoptosis
Mitoc damage - cytochrome C release - caspase activation
B1 integrin activates
MAPK cascade
Classes of CAMS
cadherins, Ig like superfamily of CAMs, integrins
cell-cell adhesion
ig like superfamily of CAMS, cadherins
calcium dependent
cadherins, integrins
ca independent
Ig superfamily
homophilic, binds to same CAMS
ig superfamily of CAMS and cadherins
heterophilic
ig superfamily of CAMS and integrins
junctions containing cadherins
adherens junction, desmosome
has cadherin, ties actin together
adherens junction
has cadherin, ties actin together
desmosome
ECM with cytoskeleton
integrins
Integrins mediate cell-cell interactions. T/F.
T weakly nga lang
number of integrin alpha and beta subunits
17 and 8
three components of ECM and their functions
collagens - structural framework for strength and resilency, proteglycans – cushions cells, adhesive matrix proteins - binds these components to receptors on cell surface
Junctions of integrins, identify connected molecules
focal adhesions (FN to actin), hemidesmosomes (IF to collagens & laminins)
Integrins trigger cell signalling through…
focal adhesion kinases
____ make up ___ to allow free passage of ions from cell-cell
connexons make up gap junctions
two molecules allowed to traverse through gap junctions
Ca and CAMP
What does NO bind to?
Guanylyl Cyclase (converts GTP to cGMP)
