Biosignaling Week 5 German

Question 1

What are the six requirements for effective signal transduction?

Answer 1

Specificity
modularity
feedback
integration
fidelity 
amplification

Question 2

what does autocrine mean

Answer 2

feedback is self stimulating

Question 3

what does paracrine mean

Answer 3

signals within organ systems and pretty localized, and also can be between organ systems

Question 4

what does endocrine mean

Answer 4

signal is sent into blood stream for a systemic response, signal travels far

Question 5

What are the four components of signal transduction?

Answer 5

1. signal
2. receptor
3. transduction pathways
4. Targets

Question 6

What the types of signals?

Answer 6

Soluble: Proteins, AAs, lipids and FAs, carbohydrates
Linked: lntegrin
Physical: mechanical(mechanoreceptors) , light(opsin), and temperature(TRP channels)

Question 7

Receptor families

-G protein-coupled receptor

Answer 7

external ligand binding activates an intracellular GTP-binding protein (G), which regulates an enzyme that generates an intracellular second messenger.
-Leads to activated enzymes

Question 8

Receptor families

-Receptor tyrosine kinase

Answer 8

ligand binding activates tyrosine kinase activity by autophosphorylation.

• Activated by themselves
• Kinase activates transcription factor, altering gene expression

Question 9

Receptor families

-Receptor guanylyl cyclase

Answer 9

ligand binding to extracellular domain stimulates formation of second messenger cyclic GMP
-Self activated

Question 10

Receptor families

-Gated ion channel

Answer 10

opens or closes in response to concentration of signal ligand or membrane potential
-self activated

Question 11

Receptor families

-Adhesion receptor (integrin)

Answer 11

Binds molecules in extracellular matrix, changes conformation, thus altering its interaction with cytoskeleton
-at plasma membrane, tells a cell about ECM, and alters conformation of cytoskeleton

Question 12

Receptor families

-Nuclear receptor

Answer 12

hormone binding allows the receptor to regulate the expression of specific genes

Question 13

Receptor families

-Cytokine receptors

Answer 13

respond to interleukins(Type I and II), TNFR, and Igs

Question 14

Name the 7 canonical receptor families

Answer 14

1. G-protein coupled
2. Receptor tyrosine kinase
3. Receptor Guanylyl cyclase
4. Ligand Gated Ion Channels
5. Adhesion
6. Nuclear
7. Cytokine

Question 15

What is Kd

Answer 15

dissociation constant for ligand binding

represents when 50% of ligand is bound to receptors

Question 16

What are the four main roles of the plasma membrane

Answer 16

1. Receptor localization
2. ligand exposure
3. Signaling complex formation
4. Endocytosis

Question 17

Why are signaling endosomes important?

Answer 17

they change the concentration of the signal ligand so that the signal with be sent more often within the cell

Question 18

What are the two types of lipid rafts

Answer 18

Caveolar: leads to caveolar mediated endocytosis
Planar: signal promotion and signal inhibition, no endocytosis

Question 19

what enzyme directs the traffic dealing with vesicles?

Answer 19

Rab GTPase

Question 20

Signal transduction order?

Answer 20

First messenger(ligand)
receptor
signal transducer (g protein)
primary effector (adenylyl cyclase)
second messenger (cyclic AMP)
secondary effector (protein kinase)
signaling cascade 
** effectors are usually enzymes**

Question 21

How do chemical rxns transfer information

Answer 21

complex formation or dissociation
structural change
Post-translational modification (allosteric mod)

Question 22

Important post-translational modifications

Answer 22

phosphorylation
ubiquitination
glycosylation
oxidation
methylation
acetylation
SUMOylation

Question 23

Common signaling cascades

there are four of them

Answer 23

1. MItogen-activated Protein Kinase (MAPK)
2. Janus Kinase-Signal Transducer and activation of Transcription (JAK-STAT)
3. PHosphatidylinostiol 3-kinase (PI3K)
4. Phospholipase C (PLC)

Question 24

Important things to know about the signaling cascades

four of them

Answer 24

• receptors activate multiple signaling cascades
• conserved signal transduction process
• variable messengers
• signals are context specific

Question 25

Mitogen-Acitvated Protein Kinase (MAPK) signaling

Answer 25

Phosphorylation of three proteins is the pathway and activated RAS then activates MAPKKK to MAPKK to MAPK, which leads to regulation of gene expression, Cell cycle progression, translation, mRNA stability, Adhesion and Migration

Question 26

Janus Kinase-Signal transducer and Activator of Transcription (JAK-STAT) signaling

Answer 26

upon ligand binding, the receptor will dimerize and the JAK will phosphorylate the tail of the receptor and then the STAT protein is phosphorylated and sent to the nucleus which leads to transcriptional modifications by the STAT protein -simplest signaling pathway

Question 27

Phosphatidylinositol 3-kinase (PI3K) signaling

Answer 27

phosphorylates a lipid (PIP2) not a protein, and then will go activate PIP3 which activates AKT which then inhibits protein synthesis, cell cycle, and cell survival

Question 28

Phospholipase C signaling

Answer 28

activated by G-protein receptor and then the alpha portion of the G protein activates phospholipase C and this takes PIP2 and cleaves it into IP3 (head of lipid) and leaves DAG which activates PKC and then IP3 activates IP3-gated calcium channel

Question 29

What are the most common targets for signal transduction?

Answer 29

nucleus -> trancription, cell division cytoskeleton-> cell structure and motility enzymes-> initiate metablic pathways receptors-> alter signal transduction transporters-> change intracellular environment ion channels -> change membrane potential

Question 30

Epinephrine signaling

Answer 30

affects vascular tone (constriction or dilation) Co-administered with local anesthetics **G-protein and PLC signaling

Question 31

Insulin signaling

Answer 31

regulates cellular division and metabolic processes transports glucose into cells, alters blood sugar, enables aerobic respiration **RTK, MAPK, PI3K signaling

Question 32

Beta adrenergic receptor

Answer 32

ligand is epinephrine and this leads to G-protein to split and the alpha subunit activates adenylyl cyclase to convert GTP to cAMP and ** leads to Smooth muscle relaxation and vasodilation

Question 33

alpha adrenergic receptor

Answer 33

norepinephrine binds to the alpha adrenergic receptor and GTP causes the alpha subunit of G-protein to activate Phospholipase C which then activates PIP2 into IP3 and DAG. IP3 leads to release of calcium of ER. **this leads to smooth muscle contraction and vasoconstriction

Question 34

Insulin signaling

Answer 34

- causes dimerization of its receptor RTK and causes its tails to auto phosphorylate, which leads to IRS-1 which recruits RAS to activate the MAPK pathway which leads to the production of proteins that alter translation. - IRS-1 also activates PI3K to activate PIP2 and activate PIP3 which activates PKB which activates GSK3 to make it inactivate glycogen to make glycogen synthase active to make glycogen.