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Bio 181: Cell Signalling


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What are included as signalling molecules?
protein, peptide, nucleotide, steroid, fatty acids, dissolved gases NO and CO. Light and odor are also signals.
Cells have __________ for signaling molecules.
Binding signal leads to a ___________ of intracellular ________________, and may include regulators of gene expression.
-2nd messengers
Most cell signals involve ___________- add phosphate to a protein (518 protein kinase genes in human cells, 1/3 proteins have Pi).
protein kinases
Cells are low in ____ and high in ____. Cells are also low in _____. Opening ion channels allows rapid signaling.
- Na+ (or Ca2+)
- K+
- Ca2+ (or Na+)
Describe features of cell signalling.
-Systems can have multiple functions including vision, memory, cell division, muscle contraction.
-Cells have receptors for signaling molecules.
-Binding signal leads to a cascade of intracellular "2nd messengers"
-Most involve protein kinases
Epinephrine: where is it produced, when is it used, and what is the biological response?
-Produced in Adenal Gland
-used during emergencies; fight or flight.
-cellular glucose and metabolism go up.
-glucogen storage and insulin response goes down.
Glucagon: where is it produced, when is it used, and what is the biological response?
-Produced by Liver
-Used for food storage between meals or skipped meals.
-Blood glucose goes up.
Insulin: where is it produced, when is it used, and what is the biological response?
-Produced by pancreas
-used after a meal
-Blood glucose goes down.
Leptin: where is it produced, when is it used, and what is the biological response?
-Produced by adipose (fat) tissue
-signals fat levels in adipose tissue
-increases fatty acid oxidation in tissues
________ and ________ regulate metabolism in our tissues, and signal our brain to reduce _________ and increase ________________.
-metabolic rates
What do cytokines do? and what are two common cytokines?
-They cause differentiation and cell division.
What's prolactin's function?
Prolactin causes epithelial cells of the breast to turn into milk producing cells.
What's erythropoietin's function?
Erythropoietin causes bone marrow progenitor cells to produce red blood cells.
__________ receptor can be expressed in bone marrow cells; add __________ and cells produce red blood cells.
What does hormone binding to a receptor cause?
It causes pre-existing transcription factors and kinases to follow their developmental program.
What are the four common signalling mehanisms, and what do they do(/are)?
Autocrine: signals to itself or same cells.

Paracrine: secretes signals to nearby cells; may be of different types

Endocrine: it's a hormone secreted into the blood.

Synaptic: sends neurotransmitters through cell to cell chemical synapse
Describe the E. coli Env Z receptor system as a model for cell signaling.
-EnvZ in the inner membrane changes shape and phosphorylates itself in response to high solute.

-The phosphate is transferred to OmpR in the cytoplasm which initiates transcription of ompF.

-Translation produces the OmpF protein which inserts into the outer membrane and prevents solute entry.
What is a receptor (R)?
cellular protein
What is a ligand (L)?
a signal that binds to a receptor
R + L = ?
List different kinds of receptor systems.
Ion Channels
enzyme-linked receptors
G protein-coupled receptors
cytoplasmic receptors
Breifly describe ion channels as a receptor.
Gated, allowing ions such as Na+, K+,Ca2+, or Cl- to enter or leave the cell.
Breifly describe enzyme-linked receptors.
-Binding ligand causes receptor to activate a protein kinase, or to bind a subcellular protein kinase.

-Transfer of phosphate changes activities of enzymes (key to most cell membrane receptor systems).
Breifly describe G protein-coupled receptors.
-Receptor is a single polypeptide that passes through the membrane seven times (also called Serpentine receptors).

-Ligand binding activates the receptor causing a G protein to bind GTP.
Breifly describe cytoplasmic receptors.
Ligands that are non-polar can diffuse through the plasma membrane and interact with cytoplasmic receptors.

Ex: Steroid hormones bind a cytoplasmic receptor which then can enter the cell nucleus and activate gene expression.
What are two ways in which drugs interact with receptors?
Agonist: binds receptor and stimulates a response; maybe even stronger than normal ligand

Antagonist: binds receptor and blocks stimulation by ligand
What are second messengers? and what do they do?
-Second messengers are indirectly generated when a ligand binds to a receptor, and they eventually are the ones to direct the response.

-second messengers amplify a signal, and frequently activate protein kinases.
What types of molecules serve as second messengers?
cAMP, inositol triphosphate (IP3) and diacyl glycerol (DAG) from phospholipids, NO, Ca++
Describe a Kinase Cascade.
A kinase cascade is a series of protein kinases that activated and inactivated as a phosphate group is passed through them. Such a cascade usually signals a biological response.
G proteins can form __(#)__ second messengers from __________.
Briefly describe the cellular response to epinephrine in muscle tissue.
This response blocks glycogen synthesis and stimulates glycogen breakdown releasing glucose for metabolism in our tissues. (Glucagon stimulates the same pathway).
What’s the function of adenylyl cyclase?
Dephosphoralate ATP to cAMP.
How are cell responses reversed?
⬢ Phosphatases remove phosphate
⬢ GTPases remove GTP from G proteins
⬢ Phosphodiesterases breakdown cAMP and cGMP
List the kinds of and functions of cell junctions.
Gap Junctions:
-Channels between cell membranes formed by proteins called connexons.
-Passage of small signaling molecules and ions permit metabolic cooperation and coordination between adjacent cells.
-Coordinated responses to signals are possible, for example in the muscle cells that regulate the regular contractions of the uterus during childbirth.

-Connections between plant cells, an extension of the ER penetrating the cell wall and connecting adjacent cells.
-Plants lack capillaries, and so nutrients and signaling molecules can directly pass between adjacent cells.
-Mesophyll and bundle sheath cells are connected by plasmodesmata allowing fixed carbon to move between tissues of the plant.
What roles to cilia play in cell signalling?
odorant receptors, neural function, development, receptors for leptin, etc.
What is hypothesised from Endothelial NO synthesis?
calorie restriction extends lifespan
Estrogen and testosterone are steroid hormones, and are most likely to bind to what kind of receptors, and why?
cytoplasmic receptors, since hormones are hydrophobic.
The endogenous GTPase activity of G-proteins serves to...
...hydrolyzes GTP returning the G protein to a pre-stimulated level of activity.
In a fight-or-flight response, epinephrine released by the adrenal glands binds to a membrane receptor on muscle cells. What are the steps that result?
1. G-protein is activated by binding GTP and activates adenylyl cyclase which produces cAMP.

2. The second messenger, cAMP activates protein kinase A which inhibits glycogen synthetase blocking glycogen synthesis.

3. Protein kinase A activates phosphorylase kinase which transfers a phosphate activating glycogen phosphorylase leading to the breakdown of glycogen and the production of glucose-1-phosphate.

4. Glucose produced from glucose-1-P stimulates glycolysis, producing energy for muscle contraction.
Direct cellular connections such as gap junctions in animal cells and plasmodesmata in plant cells permit:
second messengers produced in one cell to rapidly diffuse into and stimulate events in surrouncing cells

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