Topic 9: Cell Signaling

Question 1

What are the types of signals in the cell?

Answer 1

endocrine signals
paracrine signals
autocrine signals

Question 2

What are endocrine signals?

Answer 2

act over a long distance and are distributed through the blood stream

example: insulin (peptide hormone released from the islets of the Langerhans cells in the pancreas)

insulin signals muscle cells to uptake glucose into the muscle and adipose cells in response to high blood glucose levels

Question 3

What are paracrine signals?

Answer 3

act over short distances and are released locally

example: epidermal growth factor (EGF)

paracrine growth factor that acts on a wide variety of both epithelial and mesenchymal cells

acts to coordinate cells in a tissue

Question 4

What are autocrine signals?

Answer 4

act on the same cell that secretes them

signals released by a cell can trigger a response in same cells

Question 5

What are protein/peptide based signals?

Answer 5

protein: >25 a.a.
peptide: <25 a.a.

neurotransmitters and hormones

Question 6

What are lipid based signals?

Answer 6

sex hormones

steroids based on cholesterol

permeable to bilayer with cytoplasmic receptors

Question 7

What are small molecule signals?

Answer 7

neurotransmitters

Question 8

What are receptors?

Answer 8

receptors are almost always transmembrane proteins in the cellular membrane (the exception: steroid hormone receptors)

receptors have a ligand binding domain that is specific to the signal they receive

Question 9

How does the reception domain (ligand binding domain) promote specificity?

Answer 9

geometric compatibility: “lock + key”

chemical compatibility: stability of intermolecular forces is weak but sufficient to reduce a cellular charge

Question 10

What are ion channel coupled receptors?

Answer 10

ligand gated channel

binding of ligand causes a shape change in receptor that opens or closes a channel

e.g. postsynaptic neurotransmitter receptor

Question 11

What are G protein-linked receptors (GPCR)?

Answer 11

contains seven transmembrane pass alpha helices

N terminus is at extracellular side, folds into ligand binding domain

C terminus is cytoplasmic and associates with G proteins

ligand binding causes activation of G protein (GEF activity), then G protein communicates message into cell

G proteins can be stimulatory or inhibitory

Question 12

What are protein kinase-associated receptors?

Answer 12

receptor has kinase activity

two types: receptor tyrosine kinases and enzyme linked

Question 13

What are receptor tyrosine kinases (RTK)?

Answer 13

intracellular domain of receptor has kinase activity and auto-phosphorylation

ligand binding causes dimerization of receptors and cross-phosphorylation

Question 14

What are enzyme linked receptors?

Answer 14

ligand binding activates an associated kinase (e.g. Ser/Thr kinases)

Question 15

What is signal transduction?

Answer 15

receptor conformation change or clustering causes an intracellular message that can be communicated throughout the cell to elicit cell change

messages are relayed via a series of second messengers

allows amplification of response

allows integration of signals

Question 16

What are two types of second messengers?

Answer 16

kinase cascades

G protein cascades

Question 17

What are kinase cascades?

Answer 17

Ras/MAP K (e.g. insulin)

Ser/Thr (e.g. TGF-beta signal)

Question 18

What are G protein cascades?

Answer 18

G protein activation activates second messengers

i.e. ion second messenger (Ca2+)
i.e. CAMP second messenger

Question 19

How is G protein signaling using IP3/DAG second messengers used in light induced signaling of Rhodopsin?

Answer 19

1. A receptor is activated by the binding of its ligand. The receptor-ligand complex associates with the G protein causing displacement of GDP by GTP and dissociation of alpha and beta subunits
2. The GTP-Galpha complex then binds to phospholipase C activating is can causing cleavage of PIP2 into IP3 and DAG
3. IP3 is released into the cytosol, where it triggers calcium release
4. DAG remains in the membrane, where it activates protein kinase C

Question 20

What can messages instruct the cell to do?

Answer 20

release/absorb nutrient (eg insulin): stimulates reuptake of glucose into the blood, epinephrine triggers release of glucose into the blood

release more signals (eg neurotransmitters): opening of ion channels in the membrane can trigger an action potential

change gene expression (eg growth factors): jun transcription factor stimulates cyclin A expression

change activity of downstream effectors (eg muscle contraction): calcium release allows activity of calmodulin that signals smooth muscle contraction