Download SIGNAL TRANSDUCTION PATHWAYS Student Version Outline

SIGNAL TRANSDUCTION PATHWAYS
I. Reception
A. Plasma Membrane Receptors
i. G Protein Coupled Receptors (order the following steps)
ii.

Cytoplasmic side of receptor binds an inactive G protein.
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Enzyme’s activity and shape are altered and enzyme is activated.
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G protein functions as a GTPase enzyme, which hydrolyzes its bound GTP
to GDP, thereby inactivating the G protein.
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Activated enzyme triggers next step leading to cellular response.
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Appropriate receptor binds to extracellular side of receptor.
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Receptor is activated and changes shape.
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G protein is activated.
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GTPase activity of the G-protein allows rapid shut down of pathway when
signaling molecule is not present.
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GTP attaches to G protein, causing displacement of GDP.
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Activated G-protein dissociates from receptor and binds to a membrane
enzyme.

G protein available for resuse.
Receptor Tyrosine Kinases (order the following steps)

Dimerization causes phosphorylation of tyrosine, resulting in 6 ADP.

Intracellular relay proteins recognize activated, phosphorylated tyrosine
dimer

Receptor exists as a monomer

Each activated protein triggers a specific signal transduction pathway and a
particular cellular response.
iii.

Binding of signaling molecule (ex: growth factors) causes 2 monomers to
form dimer.

Intracellular relay proteins bind to a specific tyrosine, which activates the
relay protein.
Ligand Gated Ion Channel Receptors: (order the following steps)

Ligand dissociates from receptor, causing gates to close and preventing
further ion entry

Change in ion concentration can directly affect cellular activity.

Ligand binds to receptor, causing gate to open.

Concentration of ion rapidly changes inside the cell

Specific ions flow through channel.
B. Intracellular Receptors
Receptors found in either cytoplasm or nucleus
Chemical messenger crosses target cell’s plasma membrane (hydrophobic or small enough;
examples: steroid hormones; thyroid hormone; Nitric oxide)
Chemical messenger binds to cytoplasmic receptor protein (as opposed to receptor protein in
membrane).
Hormone-Receptor complex enters nucleus and serves as a transcription factor.
Transcription Factors determine which genes on a chromosome should be transcribed into a
protein. The steroid receptor carries out the signal transduction.
Other receptors (example: the thyroid receptor) are already in nucleus, so the signal molecule
attaches to receptor in the nucleus
II. Transduction:
A. Protein Phosphorylation and Dephosphorylation
Two key types of enzymes involved:
 Protein Kinases: enzymes that transfer phosphate from ATP to a protein
 Protein Phosphatases: enzymes that rapidly remove phosphate groups from
proteins, in a process called dephosphorylation.
Phosphorylation Cascade (order the following steps)

The third active protein kinase phosphorylates a final protein that causes a
specific cellular response.

Protein phosphatase enzymes remove phosphate groups from the proteins,
inactivating the proteins so they can be reused again.

First activated protein kinase transfers phosphate from ATP to an inactive
protein kinase #2, causing the second protein kinase to change shape.

A relay molecule activates first protein kinase by causing the protein kinase
to change shape.

The second activated protein kinase phosphorylates and activates the third
protein kinase, causing it to also change its shape.
B. Second Messengers
 Nonproteins
 Water soluble molecules or ions
 Spread via diffusion
 Carry signal initiated by the ligand
 Carry signals initiated by G protein coupled receptors or Receptor Tyrosine
Kinases
 Two most common second messengers: cyclic AMP; Ca++
Sample cAMP pathway (order the following steps)

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cAMP activates another protein, usually a protein kinase “A”
adenylyl cyclase converts ATP to cAMP
plasma membrane protein receptor activates adenylyl cyclase
The ligand epinephrine binds to plasma membrane receptor of liver cells
cAMP concentration in cytosol increases
cellular response occurs
protein kinase “A” begins phosphorylation cascade of other proteins
Sample Calcium Ion or IP3 pathway (Order the following steps)

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Plasma membrane phospholipids is broken down into DAG and IP3.
Phospholipase C is activated
Signaling molecule binds to membrane receptor
Calcium ions activate next protein in signal pathway.
Calcium ions flow out of ER.
IP3 binds to IP3 gated calcium channel receptors in ER, causing channel to
open.
Calcium levels in cytosol increase
III. Response
Response occurs in the nucleus or cytoplasm
Nuclear responses:
The receptor may originally be in the cytoplasm or already be inside the nucleus.
If receptor is originally in the cytoplasm, the ligand attaches to the receptor while it is in
the cytoplasm and then the receptor-ligand complex moves inside the nucleus.
If the receptor is originally present inside the nucleus (ex: thyroid receptor), then the
ligand itself crosses the nuclear member to form the receptor-ligand complex.
Once the receptor-ligand complex is inside the nucleus, it functions to:
1) Transcribe genes/synthesize mRNA
2) Regulate gene function (determine which genes are turned on/off)
3) Regulate many different genes at the same time
Cytoplasmic responses:
1) May regulate the activity of proteins instead of their synthesis.
2) May induce growth of cytoskeletal microfilaments (ex: the binding of mating factors
in yeast trigger signaling pathways that lead to growth of cytoskeletal microfilaments
in areas of the plasma membrane exposed to the highest concentration of mating
factor).
3) May trigger cell division.
4) May regulate metabolism
In each box, list the name of the enzyme and briefly describe its role.
Activating Enzymes
Deactivating Enzymes