Signaling Flashcards
Primary Signal/Messenger
- cells rely on them to share information with each other
- Lock and key (geometrically locked)
example: Hormone
Outline of signaling
- Reception - Signal received of signal
- Transduction- Signal is transmitted
- Response -Signal is received
What happens at the end of response?
Change in gene expression
Growth factor?
Something that enhances or induces growth
What happens in the response?
Activation of cellular response
What is a gene?
- Portion of DNA that codes information that will be active or suppressed depending on the need
- Genes are highly conserved between species
- It is not the differences in genes themselves that appear to be responsible for diversity
Cell fate determination
undifferentiated cells tale on certain fates (differentiate) during embryogenesis
What are the two driving forces in development
Cell fate determination
Morphogenesis
Morphogenesis
“Creation of ordered form”-
cell types must be organized properly into tissues, organs
Transcription Factors
changes chromatin to allow/block RNA polymerase II access to the gene
helps with gene expression
Primary Messenger signals …
stay in between cells
Secondary Messengers signals..
always inside the cells
Teratogens
Any agent that causes a structural abnormality following fetal exposure during pregnancy
Cyclopamine
Teratogen
blocks the action of smoothened
embryos exposed to cyclopamine are similar to those defective in Hedgehod signaling
one eye cow
Notch signaling- Lateral Inhibition
Cell express more delta on its surface that its neighbors
notch signaling in the surrounding cells inhibits the expression of genes required for neural differentiation
What causes the development of cancer
Protooncogenes
tumor supressors
Protooncogenes
Function as positive regulators of cell growth
induce tumors through gain of function
Tumor Suppressors
Function as negative regulations of cell growth
loss of function results in tumor growth
Receptor-mediated Signal Transduction
- GPCRs (G Protein coupled receptors)
2. Receptor Tyrosine Kinsases
The majority of hormone receptors belong to the family of receptors knows as
G-protein coupled receptors (GPCRs)
Peptide Hormones Vs steroid hormones
Peptide Hormones -can’t pass through the membrane
Steroid Hormones- hydrophobic, can pass through the cell membrane
Receptor-mediated Signal Transduction via hormones result in
regulating gene transcription
G protein
Transmembrane protein that loops around through the membrane 7 times
Types of receptor ligands
- Agonist ( full or partial)
2. Antagonist
Ligand is aniother name for
Primary messanger
Largest family of proteins in the human genome
G protein coupled receptors
over a 1000 types
Andrenergic Receptor
GPCRs
Norepinephrine
Epinephrine
Muscarinic Receptor
GPCRs
- Bind acetylcholone but are GPCRs
- Sensitive to muscarine of poisonous mushrooms
What are the three subunits of G proteins
alpha
beta
gamma
Which G protein subunit normally bind to GDP?
Alpha subunit
What normally binds to the alpha subunit?
GDP
What allows the three subunits at the end of the g protein signaling to recombine
alpha subunit hydrolyzes GTP–>GDP
IN G protein signaling what are the effector enzymes?
Adenylate Cyclase
Phosopholipase C
What happens when GDP is replaced GTP on G protein?
alpha is dissociated from beta and gamma
After Primary Messengers (ligands) bind to the membrane which enzymes increase/decrease in activity via G proteins ?
- Adenylate Cyclase
- phospholipase C
- Ca++
cAMP
3
- cyclicAMP
- Secondary Messenger
- Made by Adenylate Cyclase
(ATP –> cAMP)
What does cAMP activate
Kinases that phosphorylate enzymes that allow physiological response
(Ex. move glucose form glycogen)
Epinephrine
A Primary messenger
Can stimulate or inhibit the production of cAMP
DAG
3
- Diacylglycerol
- Secondary Messenger
- Made by phospholipase C
IP3
- Inositol 1,4,5-triphosphate
- Secondary Messenger
- Made by phospholipase C
What does IP3 do?
- Binds to the ER causing rapid release of Ca++
2. Increase in Ca++ causes the activation of protein kinases
What does DAG do?
- Activates membrane-bound protein Kinase C
- That activates enzymes
- Leads to Cellular Response
What makes the G protein active?
Binding of GTP
Properties of secondary messengers
- small
- diffusible
- non protein
- work inside the cell to trigger a downstream response
Ca++
- Secondary Messenger
2. Release from ER when IP3 binds to the membrane
Once Ca threshold is triggered…
- Ca++ binds to Calmodulin
2. Activation of Protein Kinases
Protein Kinases
enzymes that phosphorylates making things active
Protein Kinase C and their activators
DAG
Ca++
Protein Kinase A activators
cAMP
Calcium/Calmodulin dependent kinases activators
[Ca++ calmodulin]
Receptor Tyrosine Kinases (RTKs)
- Both receptors and enzymes
2. Membrane bound proteins
Receptor Tyrosine Kinases (RTKs)
4 major domains
- extracellular ligand binding domain
- transmembrane domain
- intracellular tyrosine kinase domain
- intracellular regulatory domain
Which receptors must dimerize before sending their signal?
Receptor Tyrosine Kinases (RTKs)
After tyrosine kinase dimerizes
- 6 ATPs phosphorylates the dimer
2. activated relay proteins
Receptor Tyrosine Kinase Examples
- Insulin Receptors
2. Growth Factor Receptors
Tyrosine Kinase Inhibitors are used
In treatment of cancer
Cytokine Receptors
Receptors that bind pro or anti inflammatory cytokine and control inflammation
Which receptors increases or decreases inflammation ?
Cytokine Receptors
Which receptors do not require phosphorylation?
Cytokine Receptors
Example of cytokine receptors?
growth hormone
prolactin
erythropoietin
Intracellular or nuclear receptors
- Not in membranes, in cytosol or in nucleus
2. Bind to hydrophobic molecules (steroid and thyroid)
