Transcript Chapter 11 Cellular Signaling

Cellular Signaling
Section 2-3
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Discussion Points:
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What happened?
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How did you recognize where to go?
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How does this model cell communication?
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What effect did joining the pathway have on you?
(Looking for something to indicate conformational change.)
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What problems did you encounter?
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What would have happened if someone didn’t do their
job (follow instructions) or weren’t there?
Notes Quiz:
1. List the three general steps to cellular
signaling.
2. Define Ligand.
3. Describe phosphorylation.
4. What is a protein kinase.
Two Kinds of Cell Signaling
• Local Regulators
• Secreted by the signaling cell
• influence cells in close proximity
• Hormones
• Long distance signaling; they travel through the blood
stream of humans
• also known as endocrine signaling because hormones
are secreted by special structure called endocrine
glands
• Reception- the detection by a target cell of a signaling
molecule; occurs when a signal binds to a receptor
protein on the pm of the target cell
• Transduction- the binding of the signal changes the
protein in some way (think change in shape, change in
function)
• Can be single step, or a signal transduction pathway
changes in a series of different molecules
• Response- any cellular activity!!!
Reception
Reception
• General Process
• Signal molecule is complimentary in shape to
a site on the receptor
• Ligand- general term for a molecule that
binds specifically to another larger molecule
• Causes the receptor protein to undergo a
change in shape causing a change in function
Intracellular receptors
• Inside Cell-cytoplasm or nucleus
• Signal must be hydrophobic enough and small enough
• Often receptor also carries out transduction
• All very similar in structure suggesting an
evolutionary relationship
• Examples: steroid hormones and thyroid hormones
Membrane Receptors
• Transmembrane proteins
• Transmit information from extracellular
environment to intracellular
environment by changing shape when
ligand binds
G-protein Linked Receptor
Structure
• outside area for a signal to bind
• Inside area where a G-protein binds
G-protein Linked Receptor Function
• G protein linked receptor receives the signal
• activated receptor binds the G-protein exchanging
GTP (energy, activating) for GDP
• G protein diffuses along the membrane and binds
an enzyme, allosterically activating it; the enzyme
triggers the next step in the pathway
• when the signal molecule is released the G
protein will replace GTP with GDP deactivating
itself and restoring the resting state
G-Protein-Linked Receptor
• Key Feature: ability to turn off quickly
• Where/When Used: embryonic
development and sensory reception
• Diseases: cholera, pertussis, botulism
Receptor Tyrosine Kinase
• Kinase- general term for an enzyme that
phosphorylates another protein
• Structure
• Two subunits with two signal-binding sites
outside the membrane
• span the membrane
• three typrosine aa’s on each
• separated= inactive, together= active
Receptor Tyrosine Kinase
• Function
• Signal binds
• two subunits connect with each other forming a dimer
• once bound together, the two protein subunits
phosphorylate each other
• once activated, the proteins are recognized by relay
proteins to trigger a cellular response
Receptor Tyrosine Kinase
• When/Where used: cellular growth and
reproduction
• Key Feature: because there are six activated
binding sites, it can trigger a quick massive
cellular response by activating multiple signal
transduction pathways
• Diseases: cancer
Ligand gated ion channels
• Structure- a closed ion channel when inactive, an
open one when active
• Function
• Signal molecule binds
• gate opens
• ions flow through causing a cellular response
• when the ligand dissociates, the gate closes
• When/where used: nervous system signaling
Transduction
Phosphorylation and
Dephosphorylation
• Protein kinase- protein that transfers
phosphate to another protein
• Act on proteins other than themselves
• Often act on other protein kinases
• Phosphorylation cascade- a series of
protein kinases one acting on the next
• Protein phosphatase- enzyme that rapidly
removes phosphates from proteins
• Turns activated proteins off
• Makes proteins available for reuse
Secondary Messenger
• small water soluble molecules involved in
transducing a signal
cAMP
• Receptor protein activates a G-protein
• G-protein activates an enzyme that turns
ATP into cAMP
• cAMP activates protein kinase
• Protein kinase induces a response
• Important pathway in the regulation of
water/salt balance in intestines
Calcium ions
• High concentration found outside cell and
inside ER (when compared to cytoplasm)
• Signal at membrane causes release of
calcium from ER
• Leads to a cellular response
• Important pathway in muscle contraction
Response
Response
• Enzyme activation- binding to an enzyme
changes its shape and function
• Transcription factors- activate transcription
of specific gene
Why so Many Steps
• Signal Amplification- each step of the
pathway activates more proteins than the
last leading to a larger response
• Specificity of Signaling
• Most signals are cell specific
• Some can work on multiple cells but induce
a different response in each