Biosignaling

Question 1

What is a signal transduction?

Answer 1

It is the movement of one chemical message from the substrate to the receptor.

Question 2

What are the 4 features/characteristics of signal transduction?

Answer 2

• specificity (S–R–effect)
• amplification (enzymes activate enzymes)
• desensitization (terminate signal)
• integration (what is the NET response of all the effects from each signal)

Question 3

In the specificity category, what is the difference between tissue-specific receptors and tissue-specific receptor target?

Answer 3

TSR: The receptors are only present in 1 tissue and the message can only be read by these receptors.

TSRT: The receptors are present in many types of tissues, without being the same, because even if they like the same ligand, their effect is diff.

Question 4

What are some types of signals which cells respond to?

Answer 4

Hormones, light, neurotransmitters, nutrients, antigens, pheromones…

Question 5

What are the 6 major types of receptors?

Answer 5

GPCR, Receptor tyrosine kinase, Receptor guanylyl cyclase, Gated ion channel, Adhesion receptor, Nuclear receptor

Question 6

How does the GPCR function?

Answer 6

Ligand binds to the receptor. This activates the G protein to release GDP and take in GTP, which allows mvt of the G prot. towards the AC protein (adenylyl cyclase). AC uses an ATP and converts it to a cAMP, which is used to activate Protein Kinase A. PKA phosphorylates cellular prots and a response to the ligand is read.
To terminate the ligand signal, cAMP must be degraded with cyclic nucleotide phosphodiesterase = 5’-AMP. This new substrate can no longer activate PKA.

Question 7

How does the G protein in GPCR become inactive after binding to the AC prot.?

Answer 7

The G prot. has an intrinsic GTPase, thus making GTP–GDP, turning the G alpha prot. off by itself. G alpha prot will move back to the beta-gama subunits of the G prot.

Question 8

What is an example of a secondary messenger?

Answer 8

cAMP.

Question 9

What is a secondary messenger?

Answer 9

This is when a new messenger obtained initially from a ligand will activate another protein that will translate a cellular response.

Question 10

What is the structure of the Protein Kinase A (PKA)?

Answer 10

AKAP, with two strands of inhibitor sequences, each with 1 regulatory subunit and 1 catalytic subunit

Question 11

How many cAMP are needed to activate PKA?

Answer 11

4

Question 12

What are examples of prots regulated by cAMP-PKA?

Answer 12

Hormone-sensitive lipase (TG and FA oxidation/mobilization), glycogen synthase, pyruvate dehydrogenase complex (pyruvate to acetyCoA), phosphorylase b kinase (glycogen breakdown), histones (DNA condensation)…

Question 13

For GCPR, there are 2 signal terminations that occur. Which one is the first one and which one follows?

Answer 13

1- ATP-(AC)-cAMP
cAMP-(cyclic nucleotide phosphodiesterase)-5’-AMP
–2ndary messenger

2- G protein Activation depends on GTP-GDP exchange factors and the modulators of GTPase activity. When want to turn off, intrinsic GTPase acts to deactivate GDP.

Question 14

What is the process for desensitization in signal control ?

Answer 14

Hormone binds to beta-adrenergic receptor, which makes Gs(beta)gama leave the G protein. This part of the G prot. brings in BARK, which phosphorylates the Ser residues on the carboxyl terminus of R. Then, BARK leaves and BARR binds to the phosphorylated carboxyl terminus. Receptor-BARR complex endocytoses into cell and attaches to another membrane inside. THen, BARR leaves. Receptor will dephosphorylate and return to cell surface.

Question 15

In what process is BARR and BARK used?

Answer 15

desensitization. BARR = endocytosis

BARK = phosphorylate.

Question 16

What is the difference between the Gs(alpha) subunit and the Gs(beta)gama subunit6

Answer 16

Ga= activate Adenylyl Cyclase (used to transmit a signal)
G(b)y = brings in BARK to receptor (used to terminate a signal)

Question 17

What is localization of signals?

Answer 17

Many receptors are around the cell, but some many need to be activated at a specific place of the cell and not at the opposite place; for example, cAMP produced by AC will attack the closest PKA, NOT the furthest, because the catalytic subunits of the PKA are used ‘‘locally’’.

Question 18

Another type of GPCR is the IP3 and Ca signaling. How does it function?

Answer 18

The ligand binds to the receptor, which makes the Gqs subunit kick out GDP and bring in GTP. This Gqs moves to the membrane protein Phospholipase C (PLC). PIP2 in the membrane, when next to active PLC will get cleaved into diacylglycerol and IP3. IP3 goes to the endoplasmic reticulum’s receptor-gated Ca2+ channel, which releases calcium. Calcium moves into the cytosol to Protein Kinase C, where diacylglycerol has also binded to PKC. They both activate PKC– phosphorylation of cellular prots by PKC produces responses to hormones bound to the receptor initially.

Question 19

Receptor tyrosine kinase: what is the 3 major pathways it uses?

Answer 19

MPAK, PIP3 and JAK-STAT.

Question 20

How does the receptor tyrosine kinase work?

Answer 20

For the receptor to function properly, it must have its alpha and beta subunits brought together;they have an inactive unphosphorylated tyrosine kinase domain. Then, the ligand will bind to the receptor and activate the triply phosphorylated tyrosine kinase domain. (AUTOPHOSPHORYLATED). Then, either MAPK, PIP3 or JAK-STAT pathway is used.

Question 21

What is the MAPK pathway’s steps?

Answer 21

The insulin receptor has insulin binded to it, which autophosphylates the Tyr residues. The insulin receptor phosphorylates IRD-1’s Tyr residues. Grb2 binds to the IRS-1’s P-Tyr, which makes Sos bind, then Ras. Ras has GDP released and GTP come in, activating Ras. Ras binds and activates Raf-1. Raf-1 phosphorylates 2 Ser resdues on MEK, which phosphorylates 1 Thr and 1 Tyr residue on ERK.
ERK moves into the nucleus to phosphorylate transcriptor factors (Elk1 and SRF, which join together and transcribe/translate genes)

Question 22

What is the PIP3 pathway’s steps?

Answer 22

Insulin receptor autophosphorylates when insulin binds to it. IRS-1 gets phosphorylated on its Tyr residues. IRS-1 activates PI-3K by binding to it. PI-3k converts PIP2 into PIP3, which binds to the Protein Kinase B. PKB phosphorylates the active GSK3 on its Ser residues to become inactive GSK3. When active GSK3 is present, it converts active Glycogen synthase into it inactive form phosphorylated). BUT since we want to keep the GS active, we need the inactive form of GSK3, so that glycogen synthesis from glucose is increased.

Question 23

In PIP3 pathway, other than to phosphorylate GSK3, what is another use of Protein Kinase B?

Answer 23

To stimulate the mvt of glucose from out to in, so that glycogen synthesis is possible from glucose.

Question 24

What is the JAK-STAT pathway’s steps?

Answer 24

The ligand binds to the receptor and autophosphorylates itself; JAK binds to the receptor, which gets activated and changes its shape to properly accept STAT. STAT gets phosphorylated and gets dimerized with another STAT. This dimer has NLS buldge (localizes where specific DNA is need to be transcribed) and enters the nucleus to affect gene expression.

Question 25

What function fo MAPK and JAK have in common?

Answer 25

They both modify the histones that activate or deactivate genre transcription.

Question 26

What is the forward ad reverse enzymes for PIP2–PIP3?

Answer 26

F: PI-3K
R: PTEN

Question 27

Can you explain what is cross talk/integration with a concrete learned by heart pathway? LOL

Answer 27

Insulin receptor autophosphorylates and can either affect the GCPReceptor (signal transduced into effect) or the Beta-adrenergic receptor (signal termination).

• If it affects GPCR, this prot gets phorphorylated and makes SHC bind. SHC then binds to Grb2–MAPK pathway–gene expression.
• If it affects the beta-adrenergic receptor, then the insulin receptor with its phosphates will phosphorylate IRS-1–PKB. PKB’s role is to phosphorylate… the Ser residues of the beta-adrenergic receptor. At the same time, insulin receptor will phosphorylate the Tyr residues of the beta-adrenergic receptor. This phosphorylation causes BARR to bind and endocytose the receptor into the cell; GPCR action on the gene is thus reduced to zero. Cross-talk = regulation of signal.

Question 28

What is the Receptor Guanylyl Cyclase pathway’s steps?

Answer 28

The ANF receptor’s subunits come close and enclose ANF (all in EXTRACELLULAR). Then, the INTRACELLULAR catalytic domains (gyanylyl cyclases) are stable and functional and will do GTP–cGMP. cGMP will activate Protein Kinase G.

Question 29

For the Receptor Guanylyl Cyclase, how many types of guanyly-cyclases exist? What are the molecules that drive them to convert stuff?

Answer 29

2: membrane-spanning guanylyl cyclase and soluble guanylyl cyclase.
Membrane one likes ANF (extracellular).
Soluble one likes NO (intracellular).

Question 30

How does the cGMP get activated and deactivated (enzymes)?

Answer 30

GTP–(guanylyl cyclase)–cGMP–(cGMP phosphodiesterase)–5’-GMP.

Question 31

What excites Gated Ion Channels (to open and close)?

Answer 31

• ligands

- changes in membrane potential

Question 32

What type of protein maintains the resting membrane potential constant until change is needed? What is the resting membrane potential’s range?

Answer 32

Na+K+ATPase.

-70 to -50 mV

Question 33

Do Gated Ion channels go with or against the concentration gradient of the ions (anions and cations)?

Answer 33

With: high to low.

Question 34

In Gated Ion Channels, the Na+K+ATPase brings out how many Na+ for how many K+, when the membrane potential needs to be changed?

Answer 34

3 Na+ from in to out while 2K+ from out to in = more + outside than inside. THis difference in potential makes the Gated Ion Channels to move ions with their concentration gradient.

Question 35

A type of Gated Ion Channels in neurons is the VOLTAGE GATED CHANNEL. How does it basically work?

Answer 35

When the hormone acetylcholine reaches the membrane, then Na+ channels are stimulated to bring from out to in some Na+. This leads to depolarization (less - than initially inside), which activated the signals of acetylcholine down the neuron’s axon. When large enough, the signal will depolarize the whole membrane on its way to the secretory vesicles near the synaptic cleft. This depolarization will cause the K+ channels to open and release K+ into the out, while Na+K+ATPase push 3NA+ out too, to reinitialize the membrane.
When the acetylcholine reaches the presynaptic cell and its vesicles, it traps acetylcholine and waits for VOlted-gated Ca2+ channel to release Ca2+ into the presynaptic cell, as the wave passed. The vesicles will endocytose (due to Ca2+) its content into the synaptic cleft. There, Acetylcholine binds to the acetylcholine gated receptor and Na2+ is allowed to go inside the postsynatic neuron.

Question 36

What is the difference between polarized, depolarized and hyperpolarized membranes?

Answer 36

Polarized: more - charges inside compared to outside.
Depolarized: less - changes inside compared to before state.
Hyperpolarized : TOO MUCH - inside cell.

Question 37

Basically, what is a neuronal signal?

Answer 37

Acetylcholine is the signal that attacks the receptors to provoque Na+ mvt from one neuron to the other. This mvt is the depolarization and its rehabilitation.

Question 38

Acetylcholine receptor lets anions or cations come in the neuron?
What is the structure of this receptor and how does it function?

Answer 38

Cations (Na+).

M2 helices have bulky Leu side chains. A

Question 39

What are the Adhesion receptors’s steps? (AKA Integrin)

Answer 39

The fibronectin with RGD sequence will bind to the adhesion receptor (alpha and beta subunits joined) and can affect the internal cytoskeleton (actin filaments) to change shape (cells need to know where is the lumen and where is the outside side (nutrients come from the lumen)).

Question 40

What are some characteristics of the Adhesion receptors?

Answer 40

It is composed of alpha and beta subunits.
It has a bidirectional signal transduction (external to internal or opposite).
The external integrin part has fibronectin with RGD (Arg-Gly-Asp) sequence.
The internal integrin is Talin and Vinculin will bind to the cytoskeleton and allow for cell motility.

Question 41

What are the Nuclear receptors steps?

Answer 41

The serum binding protein binds with hormone substrate. When this complex comes close to the cell, the hormone leaves the binding protein and diffuses across the plasma membrane and binds to the receptor in the nucleus. Then, the receptor changes shape with this binding and the receptor forms a homodimer or a heterodimer. These are the Hormone Response Elements (HRE) in the DNA. This binding regulates trascription of genes (increasing or decreasing the rate of mRNA formation). The mRNA will get out of the nucleus into the cytoplasm and form a new protein with altered cell function (cellular response to the hormone).

Question 42

How can the Adhesion receptor’s signals be interpreted? (bidirectional: fibronectin vs talin and vinculin)

Answer 42

When signal comes from the outside to the inside, it determines the cell’s shape and alter gene expression.
When signal comes from the inside to the outside (like talin and vinculin), the cell moves; this helps between interaction between the extracellular matrix (loose/tight) and cytoskeleton. Ex. metastasis (cancerous cells that MOVE) = talins and vinculins are targets as IMP factors for cancer therapy).

Question 43

When the dimer is in the nucleus, transcription (response) is_____.
When the dimer is in the cell membrane, the transcription is _____.

Answer 43

Slow.

Fast.