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U4L7 - Cell Signaling II
Unit 4 - Lecture 7 - Cell Signaling II - Dr. Mitchell - SUNY Upstate - Fall 2011
20
Biology
Graduate
11/22/2011

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Term
ALL TRIMERIC G-Proteins have this type of membrane receptor protein associated with them.
Definition
7-pass helix transmembrance domain receptor If trimeric G protein --> think 7 Pass!
Term
Membrane receptors utilize .....soluble ligands
Definition
water soluble ligands!
Term
second messengers often times do this
Definition
Activate a Protein kinase
Term
To modify the ACTIVITY of the protein, the protein is ...........
Definition

phosphorylated!

 

 

Note: Activity changes b/c 2 things happened (molecule has gained an extra negative charge AND/OR the molecule has changed conformation)

 

Term
After Phosphorylation, it takes (minutes, hours) for a response. Choose one
Definition

Minutes.

Note: Control of gene expression, however, takes hours Either by water soluble hormones (CREB protein) or by steroid (lipid soluble) hormones.

Term
What is Gs?
Definition
Trimeric G protein that STIMULATES adenylate cyclase
Term
What is Gi?
Definition

Trimeric G protein that INHIBITS adenylate cyclase

 

Thus, less cAMP and therefore, less active PKA

Term
What is Gq?
Definition
Trimeric G protein that STIMULATES phospholipase C
Term
2nd messengers for Gs and Gq pathways are?
Definition
Gs --> cAMP
Gq --> DAG (diacylglycerol), IP3 (inositol triphosphate), and Ca2+
Term
The amino acids to be phosphorylated in the PKA pathway are often ...(1)...and..(2)...because they contain nucleophilic...(3)...atoms that attack the electrophilic P of the phosphates.
Definition
1) Serines (Ser, S)
2) Threonine (Thr, T)
3) Oxygen
Term
What amino acid is phosphorylated in the hormone pathway that involves a dimerization of two transmembrane proteins?
Definition
Tyrosine residues have the nucleophilic Oxygens that can be phosphorylated. They undergo a transphosphorylation-autophosphorylation reaction. 
Term
Write out simple pathway to STIMULATE Protein Kinase A (PKA)

---(+)---> means stimulates
Definition
Gs-Protein --(+)--> adenylate cyclase --> converts ATP to cAMP ---(+)--> active PKA

Called PKA b/c of the "A" in Adenylate cyclase
Term
Write out simple pathway to STIMULATE Protein Kinase C (PKC)

---(+)---> means stimulates
Definition
Gq-protein --(+)--> Phospholipase C --(+)--> breakdown of phospholipids into 2nd messengers (DAG and IP3).
IP3 -(+)-> Ca2+ release from ER to cytosol
DAG + Ca2+ --(+)--> PKC

Called PKC b/c of the "C" in Ca2+
Term
Trimeric vs. Monomeric G proteins
Definition
Trimeric:
1) Alpha, Beta and Gamma subunits
2) Cell Surface receptor signals

Monomeric
1) Receptor linked (like Ras)
2) Vesicle sorting/fusion (Rab)
3) Actin cytoskeleton (Rac, Rho)
Term
How does a cell 'know' that a receptor tyrosine kinase has been activated?
Definition
When the SH2 protein (Src Homology 2 protein) binds to PHOSPHORYLATED Tyr residues, the SH2 changes conformation and this signals the cell.
Term
What is one signal resulting from an SH2-SH3 adaptor proteins phosphotyrosine binding?
Definition
One result may be the eventual stimulation of the MONOMERIC G Protein (p21-ras) encoded by the ras gene, which leads to the MAP (Mitogen Activating Protein) Kinase cascade and leads to increased Mitosis --> more cell division. If uncontrolled, tumors may grow.
Term
Why is a phosphorylation cascade prevalent in cell signaling pathways?
Definition
It allows for an AMPLIFICATION of the signal and increased regulatory sites in the pathway.
Term
Which type of receptor would the epidermal growth factor most likely be associated with?
Definition
Tyrosine Kinase Receptor b/c many growth factor pathways (cell division and/or cell differentiation) are prevalent.
Term
Compare GAP and GEF
Definition
GAP = GTPase Activating Protein
makes GTP --> GDP. Ex. INACTIVATES ras (monomeric G protein)

GEF = GTP Exchange Factor
Put GTP on ras protein and GDP drops off (ACTIVATES ras)
Term
*NOT TESTED in Unit 4*
Phosphorylating gene regulatory proteins (ie CREB) controls gene expression. CREB induces PEPCK gene. The increase in in number of PEPCK would (increase,decrease,not affect) the Km and (increase,decrease,not affect) the Vmax
Definition
not affect Km b/c structure of PEPCK is not changed (no affinity change)
Increase in Vmax b/c the gene has been amplified (more of it present and active)
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