Signal Transduction Flashcards
Why is Signal transduction required?
- Cell membrane is hydrophobic -> only permeable to small ions, hydrophobic membranes and inorganic molecules
- large molecules can’t enter
- Receptors embedded w/in cell membrane that have an extracellular and cytostolic domains
- signal binds to ECD outside of cell and changes a component w/in
- ligand doesn’t actually enter cell
4 categories of Signal transduction pathways in bacteria
- One component signal transduction systems
- Two component signal transduction systems
- ECF sigma factor
- Class III adenyly/guanylyl cyclases
Two component signal transduction
- how it works, components
- what used for
- 3 mechanisms of stimulus perception
- contains histidine kinase sensor and response regulator (with regulatory Domain (D))
- 2 protein molecules involved - one acts as sensor and other regulates gene in response
- two components communicate via His-Asp phosphotransfer
-conducts signal from external enviro to internal enviro.
3 different mechanisms of stimulus perception;
1. Periplasmic-sensing HKs
2. HKs w/ sensing mechanisms linked to transmembrane regions (stimulus perception can occur either w/ membrane helices alone or by combo of transmembrane regions and short extracellular loops)
3. Cytoplasmic-sensing HKs (either soluble or membrane-anchored)
One component Signal Transduction
- 1 protein - input and output domain linked
- Doesn’t require phosphorylating transfer
- 1 part senses, other acts as regulator
-used for internal environment
ECF Sigma Factors
- what they are
- How they work in absence and presence of a stimulus
- Sigma factors direct RNA poly to specific promoters
- In addition to primary house keeping sigma factors, bacteria may contain alternative sigma factors
- ECFs are smallest sigma factors - only have 2 domainsinvolved in interaction w/ RNA poly and w/ promoter seq.
In absence of stimulus, ECF sigma factors remain inactive by cognate anti-sigma factors
In presence of signal, anti-sigma factor releases ECF which then redirects RNA polymerase for the expression of specific genes
*are third most abundant bacterial signalling mechanisms
Adenylyl cyclase
- Catalyzes conversion of ATP to cAMP
- cAMP = secondary messenger that plays important role in signal transduction
Signal Transduction in Eukaryotes
-3 things it is required for
Required for;
- Transmission of various signals like growth factors
- communication among neighboring cells
- synchronizing cell cycle in tissue
Aberrant expression of genes required for signal transduction
- causes permanent activation of a signal transduction pathway
- disrupts normal regulation of cell cycle
- leads to uncontrolled growth (i.e. cancer)
3 major types of signal transduction pathways in eukaryotes
- Receptor has protein kinase activity in it’s cytosolic domain
a) Activated receptor activates an enzyme that leads to production of small molecules (secondary messengers)
b) activated receptor starts cascade that involves series of interactions between cytoplasmic kinases - ultimate product affects transcription - The receptor interacts w/ kinase
- Receptor interacts w/ G protein
Eukaryotic receptors w/ Kinase activity
- general features
- 3 types of protein kinases
-Inegral membrane proteins that span membrane once
-N-terminus on extracellular, C terminal on cytosolic side
-most single polypeptide (some are disulphide bonded dimers)
-cytosolic domains have protein kinase activity - add a phosphate group to the target
-receptors mainly have tyrosine kinase activity
3 types of protein kinases based on their specificity of target phosphorylation;
1. Tyrosine kinases (mainly receptor kinases)
2. Serine/threonine kinases (mainly cytoplasmic kinases)
3. Protein kinases w/ dual specificity
How do Receptors w/ kinase activity work?
-Ligand binds at extracellular domain induces dimerization of receptors
-activates kinase activity of cytosolic domain
-activated domain gets autophophorylated
Activated receptor tyrosine kinases lead to 2 different pathways;
a) activated receptor molecule activates enzyme that leads to production of small molecule (secondary mess)
b) activated receptor starts cascade that involves series of interactions between cytoplasmic kinases, the ultimate product affecting transcription
Kinase activity -> secondary molecules
- are phophlipases of kinases that act on lipids to generate second messengers
- inactivated enzyme gets activated
Kinase activity -> Cascade starts
-signal is transmitted via several cytoplasmic kinases to phosphorylate a transcritpional regulator
Eukaryotic: receptor interacts w/ kinase
-3 components
*are simpler signal transduction pathways
3 components;
1. A receptor that gets activated by dimerization. Cytosolic domain does not have kinase domain
2. A JAK kinase that associates w/ an active receptor and gets activated
-are tyrosine kinases and their substrates are only STATs
-a pair of JAK kinases associate w/ an activated receptor
3. STAT, a transcriptional regulator that gets phosphorylated by an active JAK
-they enter nucleus, bind at their target site on DNA and affect gene transcription
*Cell contains several JAKs and STATs that work in different combos
Mode of action of receptors with a kinase
- Ligand binds at extracellular domain - induces dimerization of receptors
- Receptor is activated (does NOT have intrinsic kinase activity
- JAK kinase activiated, which phophylates STAT (can then got and bind to DNA)
Eukaryotic signal transduction; Receptor interacts w/ G protein
- what is a G protein (why is it named so)
- Action of G protein
- these are serpentine receptors (contain 7 trans membrane regions)
- Ligand binding induces conformational change in receptor
- induced receptor interacts w/ G protein that contains 3 subunits (alpha, beta and lambda)
- G proteins named for their ability to bind to guanine nucleotides
- causes GDP from a subunit to be replaced by GTP
- a GTP dissociates from B y dimer
- acts upon an effector that in turn changes conc. of some small molecules in cell
- a GTP dissociates from B y dimer
SH2 domain = stretch of a.a. in protein that interacts w/ phophorylated tyrosines
Ras = G protein that is inactive when bound to GDP
