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39 Cards in this Set
- Front
- Back
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Effectors
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components of signal transduction pathways. The signal is propagated from upstream to downstream effectors.
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Second Messenger
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e.g. cAMP, DAG, IP3, Ca+2) - effectors that change concentration (increase or decrease) in response to ligand-receptor binding
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Three properties of these responses/pathways
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1. Different versions of each pathway with homologous factors for each step (pathway conservation)
2. Response to a pathway depends on cellular context. Different cells express diff targets = respond diff to same pathway. 3. Crosstalk bw pathways to regulate each other. |
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Receptors:Pathways activated
1-Tyrosine Kinase 2-7 Transmembrane 3-7 Tmem > Tyr Kinase |
Pathways activated
Ras>Phosphoinositide cAMP = Phospho Phospho |
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Serine/Threonine Kinase Receptors
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Receptors that bind TGFB homologs
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Serine/Threonine Receptor Characteristics
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Heterotrtrameric.
Ligands bind type II doublets. type I are then recruited to complex. Type I phosphorylate Smads. |
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Smads
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effector molecules for TGFB
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coSmads
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bind w receptor regulated Smads -> nucleus as Txn factors @ activate/inhibit genes
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Tyrosine Kinase receptors for dimers in response to ? binding
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Ligand binding
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TK recpt undergo this type of phosphorylation when ligand binds/dimerize
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Transautophosphorylation - P'ing yourself and each others
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Transautophosph induces a complex of what 3 effectors in Ras p-way
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Adaptor, GEF, Ras
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Adaptor prot
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1st factor recruited to TK receptor complex, recruits/allows GEF to join
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GEF (guanine nucleotide exchange factor)
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2nd after adaptor prot, recruits Ras.
-Dislodges GDP bound to Ras, who auto refills w guanidine & usually fills w GTP bc [GTP]>[GDP] in cell |
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Ras
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3rd recruited, activated by GTP binding which allows it as cofactor for Raf
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GAP (GTPase activating protein)
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DEACTIVATES Ras, causing Ras to dephosph its own GTP->GDP which prevents Ras from activating downstream kins, presence requires TK to constantly bind fresh ligand to perpetuate response
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Raf
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activated via RasGTP, then phosphors MEK
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MEK (MAP and ERK Kinase)
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phosphorylated by Raf, then phosphors MAP Kinase --> phosphors numerous prots, enzymes TXn factors etc
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Activation cascase
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Every kinase activated phosphors many more-->amplified signal as it goes, allowing tiny signal = large effect
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Steps in Ras pway?
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1. Ligand binds TK recept
2. Dimerize/Transautophosph 3. Adaptor/GEF/Ras 4. GAP - dephosph Ras 5. Ras GTP Ps MEK 6. MEK Ps MAP Kinase 7. MAP Ps multiple things... |
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cAMP Pathway - examples, characters?
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Glucagon w Liver
Adrenaline w Liver & Adipose |
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TGFB example?
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Works in development, differentiation, hematopoiesis most relevant to us.
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cAMP is (first) example of ...
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2nd messenger,
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cAMP phosphodiesterase
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deactivates cAMP by converting to AMP
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Adenylate cyclase
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converts AMP-->cAMP
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SevenTransmembraneRecepts
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activate cAMP & phosphoinositide pways, consist of 7 alpha helices
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Binding domain = helix ?, while helices ?, ?, ? actually bind ligand:
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7 is the domain, while 3,5,6 actually bind ligand
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G-proteins general (&what 3 forms)
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1st effectors of cAMP pway, alpha, beta, gamma.
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G-alpha dissociates from Beta/Gama, bound with ATP travels seeking what?
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Adenylate cyclase
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GAP domain function?
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shuts off pway via induces hydrolysis of GTP->GDP from the Ga-GTP complex; keeping it from adenylate cyclase
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adenylate cyclase function?
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AMP-->cAMP
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cAMP phosphodiesterase function?
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deactivates signal via cAMP
->AMP |
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Protein Kinase A (PKA)
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tetramer activated by cAMP, consists of two R(regulatory) units & 2 C (catalytic) units. C units dissociate & go on to phospho serine, threo residues etc
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cholera toxin action?
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inhibits GAP from shutting down pway, causing it to run out of control
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phosphoinositide signal involves who?
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PLC, PIP2, DAG, IP3, Ca+2, PKC
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PLC activated by, to ...
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activated by Goa-GTP, catalyzes the cleavage of PIP2-->IP3 and DAG
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PIP2 cleaved to produce...
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DAG & IP3
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DAG consists of..
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two fatty acyl side chains esterified to glycerol, one being Arachidonic acid
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Role of Ca+2
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released to cytosol from ER or endosome --> binds to PKC causing it to associate w plasma membrane
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PKC
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activated by DAG, then phosphos various items
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