____ are the four most common intracellular secondary messangers and ___ is what they activate.
cAMP - Protien Kinase A
cGMP - Protien Kinase G + cation channels in rod cells
DAG - Protien Kinase C
IP3 - Opens Ca2+ channels in ER
Calmodulin is a ____. An example is: " ____" which is a/an ____ that (does this) ____.
Cytosolic multipurpose switch protien that mediates the effects of Ca ions.
Calmodulin activation of Calcinuerin which is a protien phosphatase that activates Il-2
Il-2 stimulates t-proliferation
Cyclosporin is a ____ that works by ____ and is useful because ____.
Forming a complex with cyclophilin which inhibits calcineurin
Knocks down immune sys by preventing Il-2 release/activation
___ are the 7 signaling steps of the chemoattractant to cAMP
1. cAMP reception activates G-prot
2. G- prot activates Adenylate cyclase
3. cAMP diffuses out of cell into media
4. Internal cAMP inactivates external receptor
5. Another G-prot stimulates Phospholipase C
6. IP3 induces Ca2+ release
7. Ca2+ induces extension of psuedopodia
___ is the tertiary structure of a GCR and ___ are the parts that interact with the G-prot.
7 transmembrane alpha helices with 4 extracellular loops and 4 intracellular loops.
Loops 3 and 4 (sometimes 2) interact with G-prot.
____ is a second messenger for Adenylyl cyclase.
____ is a second messanger for Phospholipase C
IP3 and DAG
___ is a second messenger for cGMP phosphodiesterase.
Phospholipase C is a/an ____ to ____ and produces _____ when activated.
Effector protien to G-protien
IP3 and DAG
IP3 and DAG are ____ that act on ____ to ____.
secondary messnagers that act on Ca2+ Channels (IP3) and activate Protien Kinase C (DAG) which phosphorylates various enzymes and receptors, altering thier activity.
Epo is a/an ____ that ____ specifically ancts on CFU-E which are ____.
Growth factor that stimulates differentiation in hematopoietic stem cells specifially in Colony Forming Units which are erythroid progenitor cells
Epo stimulates growth/differentation in CFU-e by ____.
Inducing trx of anti-apoptotic factors allowing the cells to RBC's
____ is the signalling pathway of Epo.
Epo (ligand) --> EpoR --> JAK --> STAT, Ras/MAP, Phospholipase C, and PI3 Kinase which lead to trx activation.
____ is the tertiary structure of a Cytokine Receptor and ____ are the conformational changes post ligand binding.
Homodimer with extracellualr ligand receptor irreversably connected to cytosolic JAK prot which is activated by dimerizing after ligand binds receptor. This causes the the JAK kinases to phosphorylate eachother on a Tyr residue at the activation lip. This increases the ability of ATP to bind and subsequent Tyr residues are phosphoylated creating docking sites for the inactive STAT monomers (trx factor - dimerizes with another STAT prot once phosphorylated = active)
RTK vs Cytokine Receptor
RTK = Different monomers which form heterodimers or homodimers when bound by a ligand. The ligand induces a loop in the cytosolic domain which interacts with the other RTK activating a protein similiar to JAK (only this is part of Cytokine)
____ is an example of an RTK in humans. There __#__ types which _____ bind to various ____.
4 which differentially bind to various EGF
____ are unique feartures of HER2.
It is in a preactivated state and can form heterodimers with HER 1, 3, and 4. HER3 can only signal when bound to HER2 (lacks functional kinase domain)
Why is HER2 over expression in breast cancer patients makes it worse?
HER2 make the cell sensitive to low levels of any factor of the EGF family. Levels that would not stimulate growth with normal HER2 levels.
_____ is a drug used in the treatment of cancer and works by ____.
_____ is a monoclonal antibody used against ____. This is a good drug because it is _____ to the _____ element of HER2
RAS vs G-prot
Ras is monomeric
How is Ras activated?
RTK binds ligand and dimerizes phosphorylating cytosolic tyrosine residue
GRB2 (comprised of SH2 and SH3) binds Sos (SH3 specically binds Sos)
Sos binds inactive Ras causing GDP to dissociate and GTP to bind
What is the Ras pathway?
Ras is activated
Recruits and binds/activates Raf - Raf is activated because the 14-3-3 protein that stabalizes Raf in its inactive form is dephosphorylated
Hydrolysis of the Ras GTP --> GDP releases the active Raf from Ras
Raf phosphoryaltes MEK's activation lip
MEK phosphoylates MAP kinases activation lip
MAP kinase dimerizes and translocates to nucleus
MAP kinase phosphorylates many different prot. including nuclear trx factors
What is the MAP kinase pathway?
It is activated via Ras-Raf
Dimerizes in cytosol
activates p90RSK by phosphorylating its activation lip
MAP kinase and p90RSK both then move to nucleus
p90RSK phosphorylates/activates SRF (a trx factor)