previously on bio308
DESCRIPTION
Previously on Bio308. Graves’ Disease data activating and negative feedback loops are ‘fine’ Therefore: Hypothesis 1 not supported Not an extracellular signaling problem Move to Hypothesis 2: Cell Interpreting Signal Incorrectly Background on Receptor Activation - PowerPoint PPT PresentationTRANSCRIPT
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Previously on Bio308Graves’ Disease data
activating and negative feedback loops are ‘fine’ Therefore: Hypothesis 1 not supported
Not an extracellular signaling problem
Move to Hypothesis 2: Cell Interpreting Signal IncorrectlyBackground on Receptor Activation*What does it takes to be in a membrane
and to be a receptor
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Other mechanisms that regulate protein function
•Compartmentalization•Change in rate of synthesis
Common traits?
•Cleavage•Phosphorylation/dephosphorylation
Common traits?
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Receptor’s role (summary)Able to transduce signal because of:
•Placement in membrane (span it)•Ability to bind ligand•Ligand -induced conformational changes
So the signal ‘gets in’ without physically crossing membrane
BUT How do you go from a shape change to causing a change in gene expression?
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Surface toNucleus:Types of signaling proteins
MBoC4 Fig15-16
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Thyroid
What is constitutive activity?
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Cascade examples
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(not trimeric) G protein switch
Note the dramatic shape change depending upon thebinding partner(s)
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cAMP 2nd messenger
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Other 2nd messengers
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cAMP dep. Protein Kinase
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After activation
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Transcriptional activation
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Others
Your summaries go here
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On to Off
Hyper activity is the problem in Graves’ disease-- What ‘should’ happen to each component of the
cascade to make the cascade turn off?
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BUT Internal signaling in Graves’ Patients is fine…
There goes another perfectly good hypothesis, rejected due to data.
Next on Bio 308 (class cancelled on Thurs. Use time to catch up)
Graves’ disease: Comparing information from other situationsand disease specific information to come up withanother hypothesis for the molecular basis of this disease
CausesHow does it all add up?
TreatmentsIntroduction to paper discussion: