Exam 2 General Knowledge 10-18 Flashcards
What is the purpose of signal transduction?
To coordinate cell metabolism, growth, and development
To ensure homeostasis among tissues and organs
The respond to external stimuli (light,pressure, and heat)
What is the pathway of signal transduction cascade?
A ligand binds to receptor
Transduction happens which relays the message
There is a response
Does cAMP go through amplification?
NO
What is juxtacrine signaling?
Cell-cell contact
What is endocrine signaling?
Hormones secreted into the bloodstream
They have a low concentration
A high-affinity receptor, response time minutes to hours
What is paracrine signaling?
Secreted ligands target nearby cells
High local concentration
Low affinity receptor, response time is seconds to minutes
What is synaptic signaling?
Neuronal signaling
Synapse between neuron cells/very short distance
Very high local concentration
Very low affinity receptor happens in milliseconds
A special type of paracrine signaling
What is autocrine signaling?
Sender and target are the same cell
Response time similar to paracrine (seconds to minutes)
What are the secreted molecules of signaling?
They are the first messangers and ligands for receptors
What are intracellular receptors?
Only used for steroid hormones, thyroid hormones, or vitamins. They need to be hydrophobic
Can intracellular hormones control gene expression?
Yes, they form a dimer and eventually get into the nucleus and can control gene expression
What type of motif is the thyroid nuclear receptor?
A zinc finger
Where is the hormone bound on the structure of the thyroid receptor-DNA complex?
The middle part of the bottom part of the motif, they cause a conformational change which makes it become a dimer
What are the major cell-surface receptors?
Ligand-gated ion channels
Enzyme-linked or catalytic receptors
Cytokine family receptors
GPCRs
What are secondary messangers?
They are small molecules that are not proteins that are a cause of the first messengers. They happen intracellularly.
What does downstream signaling control?
Protein phosphorylation
What does protein phosphorylation do?
Induce conformational change
Promote or disrupt protein-protein interaction
It also causes large assemblies of proteins called scaffold, adaptor or anchoring proteins
Second way to control downstream signaling controls
GTP-binding regulatory proteins
GTP-binding regulatory proteins
GTP causes a signaling, get dephosphorylated then turns off but can get restarted again by GTP re-entering
GTP BOUND STATE IN ON
Which form of GTP-binding regulatory proteins interacts strongly with downstream signaling proteins?
The on state or the GTP bound form
What is Ras?
A type of monomeric G-proteins that causes cell proliferation and if a mutation occurs then it will most likely cause cancer
What are the two ways to terminate a signal?
Changing the amount of message (SERT)
Receptor loss or desensitization (lower response to the same agonist concentration)
Ligand gated ion channels are usually involved in what type of signaling?
Neuronal signaling
Besides receptor internalization, another way to terminate the signaling form receptor tyrosine kinase could be?
Protein phosphatase as part of a protein phosphorylation cycle
Receptor tyrosine kinase activates what well known signaling cascade?
Ras / MAP kinase signaling cascade
What is Ras-activating protein
GEF or guanine exchange factor
What is Ras?
Ras is a monomeric G protein which turns GDP into GTP
Activated Ras binds and activated MAP3K which signals the cascade of what
MAP-kinase-kinase-kinase
MAP-kinase-kinase
MAP-kinase -> to do a signal
Adaptor protein of Ras
Grb2
What does GPCRs have activity and amplification wise
GEF activity and Big amplification
Which subunit of the trimeric G protein is similar to the structure of monomeric G protein
G alpha
What does pleiotropic mean?
The same cytokine can have different target cells and receptors with different biological outcomes
Are cytokines redundant?
Yes, different cytokines can produce the same effect
What is cascade effect?
Cytokines can stimulate the production of other cytokines
What are chemokines
Cause cell migration during development, immune response, inflammation and cancer
What are chemokine receptors?
GPCRs
What do interferons do?
They interfere with viral replication also in regulation of immune response
Are cytokines a good therapeutic target?
yes, because of their anti-inflammatory pathways with could help with pathological pain from inflammation such as peripheral nerve injury
What happens when cytokine receptors are overexpressed?
They can cause tumor cells and are being looked at therapeutically to help suppress this
What are the cytokine receptors?
- Immunoglobulin family (Ig)
- Hemopoietic growth factor (type 1) family
- Interferon (type 2) family
- Tumor necrosis factors (TNF) (type 3)
- GPCRs
- Interleukin-17 receptor (IL-17R) family
How many chemokines are in the human family and how many receptors
There are 46 protein chemokines and 23 GPCR receptors
Cytokine receptors
They have cross-reactivity so they can have different cytokines bind to the same receptor
Type 1 cytokine receptor intracellular domain (spider)
A huge complex inside of the cell with up to 600 residues, they are very atypical
how to terminate a signal
rapid reducing the message by use of SERT
breakdown of enzymes by acetylcholine esterase
less signal over time but with the same concentration
RTKs
receptor tyrosine kinases that leads to phosphorylation of downwards signaling
What activates Ras/MAP kinase?
RTK receptor tyrosine kinases
When Ras is activated what does it do?
Activates cell proliferation, migration, transformation, survival but mutations can lead to cancer
What are the three Ras genes?
HRas, Kras, Nras
what are cytokines?
small proteins used to control growth and immune system cells to execute inflammation responeses
pleiotropic…..
the same cytokine can bind to different receptors and have a different effect
redundant
when different cytokines produce a similar effect
cascade effect
cytokines can stimulate the production of other cytokines
TNF-a
tumor necrosis factor that gets released upon infection from macrophages
Chemokines do what?
cell migration and theyre also called CXCL8
What is Icam and LFA-a
Where leukocytes go through rolling adhesion and stop because of the extracellular receptor Icam
Siltuximab
cancer drug which inhibits IL-6
Tocilizumab and Sarilumab
cancer drugs which inhibits IL-6 receptor
Adaptive immunity
Remember and specific respond slower (B and T-cells)
Innate immunity
respond much faster non-specific and have no memory
What are the ways that GPCRs terminates signaling
Phosphorylation of G-protein coupled receptor
b-arrestin
internalization in clathrin-coated pit
recycling or degradation
Gproteins and who they effect in GPCRs
Gs and Gi both effect adenylyl cyclase -> cAMP -> PKA
Gq effects phospholipase C - Diacylglycerol OR IP3 -> PKC OR IP3 receptor -> CALCIUM
CaM or calmodulin does what?
A small protein that binds to excess calcium and releases it
ori?
Origin of replication
What is topoisomerase do?
Essential for termination
What is p53?
A tumor suppressant protein
What do methotrexate and 5-flurouracil do?
They inhibit DNA replication to make sure the tumor cant keep growing
BCR-ABL what is it?
Causes cancer and shorten chromosome length
What is chromatin?
a long chain of wound up dna histones
epigenetics
post-transloational modifications of histones
What do HATs do?
They open up dna on a histone (acetylation)
What do HDACs do?
They wind the dna back up on the histone (deacetylation)
Transcription
Makes mRNA
Translation
mRNA goes through a ribosome and adds codons
Chaparone
Helps fold DNA
Misfolded proteins are called what?
Aggregation
Posttranslational modifications (PTMs) do what?
They add complexity to the proteome
What do large aggregates cause?
Can cause alzheimers, parkinsons, or hunningtons
Ubiquititin-proteasome proteolysis
A process that is targeted for degredation as part of cellular function
Lysosomal degredation
membrane-bound organelles containing proteases that can degredate exogenous proteins or aged/damaged organelles
Autophagy
Self engulfing process that gets rid of trash / defective organelles
Defective autophagy casues
alzheimers
Targets protein degredation by the proteasome, whats it made of
2x 19s complex and 1x 20s core complex
Ubiquitin-proteqsomal system process
E1 (activating), E2 (conjugating), E3 (ligase),need at least 4 ubiquitin molecules to be able to degrade
What activity does the 20s proteasome have?
Trypsin, caspase and chymotrypsin
Oxidative stress and proteasome
disassembles the 19s complex and leaves the 20s complex to degrade oxidized proteins
degron
recognition sequence or structure for an E3 ligase
Bortezomib
A cancer drug, the first proteasome inhibitor
