Dr. Kevin Ahern - Oregon State...

Hormones and Signal Transduction

Dr. Kevin Ahern

Signaling• Outline


Background


BackgroundMembranes


BackgroundMembranesHormones & Receptors


BackgroundMembranesHormones & ReceptorsSecond Messengers

Signaling• Introduction


Needs of a Multicellular Organism


Needs of a Multicellular OrganismResponding to Environment


Needs of a Multicellular OrganismResponding to EnvironmentFood Status


Needs of a Multicellular OrganismResponding to EnvironmentFood StatusDanger


Needs of a Multicellular OrganismResponding to EnvironmentFood StatusDangerGrowth


Needs of a Multicellular OrganismResponding to EnvironmentFood StatusDangerGrowthInjury


Coordination of Cellular/Tissue Responses


Coordination of Cellular/Tissue Responses

Signaling

Signaling• Membranes

Organization of Bilayer Around Cell


Lipid Bilayer Prevents Entry of Most Molecules




Lipid Bilayer




Lipid Bilayer




Lipid Bilayer


Information must move across membrane



Lipid Bilayer


Information must move across membraneSignal Transduction

Signaling

Signaling Simplest Signaling


Signal


Signal Response

Nerve System Signaling

Hormones and Signal Transduction• Hormones


Hormones Communicate Messages


Hormones Communicate MessagesHormones are Made in One Part of the Body


Hormones Communicate MessagesHormones are Made in One Part of the BodyExert Effects in Other Part of Body


Hormones Communicate MessagesHormones are Made in One Part of the BodyExert Effects in Other Part of BodyFirst Messengers of a Multi-component Message


Hormones Communicate MessagesHormones are Made in One Part of the BodyExert Effects in Other Part of BodyFirst Messengers of a Multi-component MessageNumerous Chemical Forms



Thyroid Hormone



Epinephrine

Thyroid Hormone



Epinephrine

Thyroid Hormone

Epidermal Growth Factor



Epinephrine

Thyroid Hormone

Epidermal Growth Factor

Progesterone

Hormones and Signal Transduction• Introduction


Cellular Signaling Has Complexity


Cellular Signaling Has Complexity Responses Aimed at Benefitting Organism

Hormones and Signal Transduction• Binding to Receptor



Steroid Hormones Diffuse Through Membrane


Steroid Hormones Diffuse Through MembraneCytosolic Receptor



Receptor Binding Inside Cell







Non-steroid Hormone



Receptor Binding Outside of Cell


Non-steroid Hormone



Receptor Binding Outside of Cell

Numerous Internal Message Carriers


Non-steroid Hormone

Hormones and Signal Transduction• Receptors


Interaction of Hormone with Receptor Changes Receptor


Interaction of Hormone with Receptor Changes ReceptorReceptor Change Alters Interactions with Other Proteins


Interaction of Hormone with Receptor Changes ReceptorReceptor Change Alters Interactions with Other Proteins

Changes on Hormone Binding

Hormones and Signal Transduction• Membrane-bound Receptors

G-Protein Coupled Receptor

Hormones and Signal TransductionG-protein Coupled Receptors (GPCRs)


Almost 800 Genes in Human Genome


Almost 800 Genes in Human Genome460 Olfactory


Almost 800 Genes in Human Genome460 Olfactoryβ-adrenergic Receptor



Membrane Bound



Membrane BoundSeven Transmembrane

Domains




Domains

Extracellular Domain




Domains

Extracellular Domain

Intracellular Domain

GPCR Action Cycle

GPCR Action Cycle

Hormone

Binding of Hormone

Hormone

Binding of Hormone

Hormone Structural Change of Receptor

Binding of Hormone


Replacement of GDP by GTP

Binding of Hormone


Replacement of GDP by GTPActivation of an Enzyme

Binding of Hormone


Replacement of GDP by GTPActivation of an Enzyme

Return to Original

State

Hormones and Signal Transduction• Receipt of Message


Membrane Receptor Proteins Internalize Message


Membrane Receptor Proteins Internalize MessageActivate Synthesis of Second Messengers



Inositol 1,4,5 Trisphosphate (IP3)




Cyclic AMP (cAMP)




Cyclic AMP (cAMP)

Ca++

Ca++

Ca++Ca++

Ca++

Ca++

Calcium Ions




Cyclic AMP (cAMP)Cyclic GMP (cGMP)

Ca++

Ca++

Ca++Ca++

Ca++

Ca++

Calcium Ions


Membrane Receptor Proteins Internalize MessageActivate Synthesis of Second MessengersCovalent Modification of “Downstream” Proteins



Ca++

Ca++

Ca++Ca++

Ca++

Ca++

Calcium Ions


Membrane Receptor Proteins Internalize MessageActivate Synthesis of Second MessengersCovalent Modification of “Downstream” ProteinsAlteration of Gene Expression



Ca++

Ca++

Ca++Ca++

Ca++

Ca++

Calcium Ions


Membrane Receptor Proteins Internalize MessageActivate Synthesis of Second MessengersCovalent Modification of “Downstream” ProteinsAlteration of Gene ExpressionChange of Enzyme Activities



Ca++

Ca++

Ca++Ca++

Ca++

Ca++

Calcium Ions

Hormones and Signal Transduction• GPCRs and G-Proteins


βγ

GPCR


βγ

GPCR

Resting State


G-Proteins Bind Guanine Nucleotides (GDP and GTP)

βγ

GPCR

Resting State


G-Proteins Bind Guanine Nucleotides (GDP and GTP)Heterotrimeric - α,β,γ Subunits

βγ

GPCR

Resting State


G-Proteins Bind Guanine Nucleotides (GDP and GTP)Heterotrimeric - α,β,γ SubunitsAssociate with GPCRs

βγ

GPCR

Resting State


G-Proteins Bind Guanine Nucleotides (GDP and GTP)Heterotrimeric - α,β,γ SubunitsAssociate with GPCRsAltered by GPCR’s Binding of Hormone

βγ

GPCR

Resting State



βγ

GPCR

Resting State

Epinephrine



βγ

GPCR

Resting State

βγ

GPCREpinephrine

Epinephrine



βγ

GPCR

GTP GDPResting State

βγ

GPCREpinephrine

Epinephrine



βγ

GPCR

GTP GDPResting State

βγ

GPCREpinephrine

Epinephrine

+

βγ

GPCR

Active

Epinephrine

Hormones and Signal Transductionβ-adrenergic Receptor Signaling

Creation of the Second Messenger





Adenylate Cyclase


Also Membrane Bound


Adenylate Cyclase


Also Membrane Bound

Adenylate Cyclase


Adenylate Cyclase


Activated by binding to α-subunit of G-protein

Also Membrane Bound

Adenylate Cyclase


Adenylate Cyclase


ATP

cAMP + PPi


Also Membrane Bound

Adenylate Cyclase


Adenylate Cyclase


ATP

cAMP + PPi


Second Messenger

Also Membrane Bound

Adenylate Cyclase


Adenylate Cyclase


ATP

cAMP + PPi


Second Messenger

Also Membrane Bound

Adenylate Cyclase

Transmits Signal


Adenylate Cyclase

Hormones and Signal Transduction• Actions of the Second Messenger

4 cAMP


Protein Kinase A

4 cAMP


Protein Kinase A

(Inactive)

4 cAMP


Protein Kinase A

(Inactive)

4 cAMP


Protein Kinase A

(Inactive)

4 cAMP

Catalytic Subunits


Protein Kinase A

(Inactive)

4 cAMP

Regulatory SubunitsCatalytic Subunits


Protein Kinase A

(Inactive)

4 cAMP Activated


Protein Kinase A

(Inactive)

4 cAMP Activated


Protein Kinase A

(Inactive)

4 cAMP Activated

Activity Altered

by Phosphorylation

Metabolic Melody

Metabolic Melody

The Tao of Hormones(To the tune of "The Sound of Silence")

Copyright © Kevin Ahern

http://www.davincipress.com/taohormones.zip

http://www.davincipress.com/professional.html



Biochemistry my friendIt's time to study you again

Mechanisms that I need to knowAre the things that really stress me so

"Get these pathways planted firmly in your head,"Ahern said

Let's start with ep-inephrineMembrane proteins are well knownChanged on binding this hormoneRearranging selves without protest

Stimulating a G alpha STo go open up and displace its GDP

With GTPBecause of ep-inephrine

Active G then moves a ways Stimulating ad cyclase

So a bunch of cyclic AMP Binds to kinase and then sets it free

All the active sites of the kinases await Triphosphate

Because of ep-inephrine





Biochemistry my friendIt's time to study you again

Mechanisms that I need to knowAre the things that really stress me so

"Get these pathways planted firmly in your head,"Ahern said

Let's start with ep-inephrineMembrane proteins are well knownChanged on binding this hormoneRearranging selves without protest

Stimulating a G alpha STo go open up and displace its GDP

With GTPBecause of ep-inephrine

Active G then moves a ways Stimulating ad cyclase

So a bunch of cyclic AMP Binds to kinase and then sets it free

All the active sites of the kinases await Triphosphate

Because of ep-inephrine

Muscles are affected then Breaking down their glycogen So they get a wad of energy In the form of lots of G-1-P

And the synthases that could make a glucose chain All refrain

Because of ep-inephrineNow I've reached the pathway end

Going from adrenalin Here's a trick I learned to get it right Linking memory to flight or fright

So the mechanism that's the source of anxious fears Reappears

When I make ep-inephrine



Date post:	19-Jul-2020
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