Hormones and Signal Transduction...

113
Hormones and Signal Transduction II Dr. Kevin Ahern

Transcript of Hormones and Signal Transduction...

Page 1: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones and Signal Transduction II

Dr. Kevin Ahern

Page 2: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• G-Protein Coupled Receptors Outline

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Hormones  and  Signal  Transduction• G-Protein Coupled Receptors Outline

Receptor G-Proteins Protein Kinase A Kinase Cascade Turning Signal Off The Coffee Connection

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Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

ATPcAMP

PKA-RegPKA

GS-P GSPKPK-P

GP-bP-GP-a

GlycogenxGlycogenx-1

Glucose-1-phosphate

Page 5: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

ATPcAMP

PKA-RegPKA

GS-P GSPKPK-P

GP-bP-GP-a

GlycogenxGlycogenx-1

Glucose-1-phosphate

1

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Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

ATPcAMP

PKA-RegPKA

GS-P GSPKPK-P

GP-bP-GP-a

GlycogenxGlycogenx-1

Glucose-1-phosphate

1

2

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Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

ATPcAMP

PKA-RegPKA

GS-P GSPKPK-P

GP-bP-GP-a

GlycogenxGlycogenx-1

Glucose-1-phosphate

1

23

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Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

ATPcAMP

PKA-RegPKA

GS-P GSPKPK-P

GP-bP-GP-a

GlycogenxGlycogenx-1

Glucose-1-phosphate

1

234

Protein Kinase A

Page 9: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

ATPcAMP

PKA-RegPKA

GS-P GSPKPK-P

GP-bP-GP-a

GlycogenxGlycogenx-1

Glucose-1-phosphate

1

234

5Protein Kinase A

Phosphorylase Kinase

Page 10: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

ATPcAMP

PKA-RegPKA

GS-P GSPKPK-P

GP-bP-GP-a

GlycogenxGlycogenx-1

Glucose-1-phosphate

1

234

55aProtein Kinase A

Phosphorylase KinaseGlycogen Synthase

Page 11: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

ATPcAMP

PKA-RegPKA

GS-P GSPKPK-P

GP-bP-GP-a

GlycogenxGlycogenx-1

Glucose-1-phosphate

1

234

55a

6

Protein Kinase A

Phosphorylase Kinase

Glycogen Phosphorylase

Glycogen Synthase

Page 12: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

ATPcAMP

PKA-RegPKA

GS-P GSPKPK-P

GP-bP-GP-a

GlycogenxGlycogenx-1

Glucose-1-phosphate

1

234

55a

6

7

Protein Kinase A

Phosphorylase Kinase

Glycogen Phosphorylase

Glycogen Synthase

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Hormones  and  Signal  Transduction• PKA Activation

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Hormones  and  Signal  Transduction• Turning Off β-adrenergic Receptor Signaling

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Hormones  and  Signal  Transduction• Turning Off β-adrenergic Receptor Signaling

Turning off the Signaling Pathway

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Hormones  and  Signal  Transduction• Turning Off β-adrenergic Receptor Signaling

Turning off the Signaling Pathway

β-adrenergic Receptor

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Hormones  and  Signal  Transduction• Turning Off β-adrenergic Receptor Signaling

Turning off the Signaling Pathway

β-adrenergic ReceptorG-Protein

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Hormones  and  Signal  Transduction• Turning Off β-adrenergic Receptor Signaling

Turning off the Signaling Pathway

β-adrenergic ReceptorG-ProteincAMP

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Hormones  and  Signal  Transduction• Turning Off β-adrenergic Receptor Signaling

Turning off the Signaling Pathway

β-adrenergic ReceptorG-ProteincAMPProtein Kinase A

Page 20: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• Turning Off β-adrenergic Receptor Signaling

Turning Off β-adrenergic Receptor

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Hormones  and  Signal  Transduction• Turning Off β-adrenergic Receptor Signaling

Turning Off β-adrenergic ReceptorExterior of Cell

Cytoplasm

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Hormones  and  Signal  Transduction• Turning Off β-adrenergic Receptor Signaling

Turning Off β-adrenergic Receptor

G-Protein Receptor Kinase

ATP ADP

PO4

=

Exterior of Cell

Cytoplasm

Page 23: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• Turning Off β-adrenergic Receptor Signaling

Turning Off β-adrenergic Receptor

PO4

=

ArrestinG-Protein Receptor Kinase

ATP ADP

PO4

=

Exterior of Cell

Cytoplasm

Page 24: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• Turning Off β-adrenergic Receptor Signaling

Turning Off β-adrenergic Receptor

PO4

=

ArrestinG-Protein Receptor Kinase

ATP ADP

PO4

=

Exterior of Cell

Cytoplasm

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Hormones  and  Signal  Transduction• Turning Off β-adrenergic Receptor Signaling

Turning Off β-adrenergic Receptor

Blocks andFavors Endocytosis

PO4

=

ArrestinG-Protein Receptor Kinase

ATP ADP

PO4

=

Exterior of Cell

Cytoplasm

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Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

G-protein Inactivation

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Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

G-protein Inactivation

Auto-regulating

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Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

G-protein Inactivation

Auto-regulatingInherent GTPase Activity

Page 29: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

G-protein Inactivation

Auto-regulatingInherent GTPase Activity

Page 30: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

G-protein Inactivation

Auto-regulatingInherent GTPase Activity

Hydrolysis

Phosphate

Page 31: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

G-protein Inactivation

Auto-regulatingInherent GTPase Activity

Hydrolysis

Phosphate

Page 32: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

G-protein Inactivation

Auto-regulatingInherent GTPase Activity

βγ

Hydrolysis

Phosphate

Page 33: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

G-protein Inactivation

Auto-regulatingInherent GTPase Activity

βγ

Hydrolysis

Phosphate

βγ

Page 34: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

G-protein Inactivation

Auto-regulatingInherent GTPase Activity

βγ

Hydrolysis

Phosphate

βγ

Return to Resting State

Page 35: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

G-protein Inactivation

Auto-regulatingInherent GTPase Activity

βγ

Hydrolysis

Phosphate

βγ

Return to Resting State

Adenylate Cyclase Inactivated - no more cAMP

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Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

PO4=

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Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

PO4=

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Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

PO4=

PO4=

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Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

PO4=

PO4=

X

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Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

cAMP

PKA

GS-PPK-P

P-GP-a

GlycogenxGlycogenx-1

Glucose-1-phosphate

PO4=

Page 41: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

cAMP

PKA

GS-PPK-P

P-GP-a

GlycogenxGlycogenx-1

Glucose-1-phosphate

PO4=

Phosphodiesterase

Page 42: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

PKA

GS-PPK-P

P-GP-a

GlycogenxGlycogenx-1

Glucose-1-phosphate

PO4=

Phosphodiesterase

AMP

Page 43: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

PKA

GS-PPK-P

P-GP-a

GlycogenxGlycogenx-1

Glucose-1-phosphate

PO4=

Phosphodiesterase

AMP

Becomes Inactive

Page 44: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

cAMP

PKA

GS-PPK-P

P-GP-a

GlycogenxGlycogenx-1

Glucose-1-phosphate

PO4=

Phosphodiesterase

AMP

Page 45: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

cAMP

PKA

GS-PPK-P

P-GP-a

GlycogenxGlycogenx-1

Glucose-1-phosphate

PO4=

Phosphodiesterase

AMP

Phosphodiesterase is Inhibited by Caffeine

Page 46: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

cAMP

PKA

GS-PPK-P

P-GP-a

GlycogenxGlycogenx-1

Glucose-1-phosphate

PO4=

Phosphodiesterase

AMP

Phosphodiesterase is Inhibited by Caffeine

Drinking Coffee Givesa Small Boost to

Blood Glucose by Keeping cAMP Levels

Higher

Page 47: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Hormones  and  Signal  Transduction• β-adrenergic Receptor Signaling

PKA

GS-PPK-P

P-GP-a

GlycogenxGlycogenx-1

Glucose-1-phosphate

PO4=

Page 48: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Receptor  Tyrosine  Kinases  (RTKs)

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Receptor  Tyrosine  Kinases  (RTKs)

RTKs are Membrane Bound Proteins that Phosphorylate Tyrosines

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Receptor  Tyrosine  Kinases  (RTKs)

RTKs are Membrane Bound Proteins that Phosphorylate TyrosinesRTKs Play Important Roles in Regulating Cell Proliferation

Page 51: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Receptor  Tyrosine  Kinases  (RTKs)

RTKs are Membrane Bound Proteins that Phosphorylate TyrosinesRTKs Play Important Roles in Regulating Cell ProliferationDimerization Important for Activity

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Receptor  Tyrosine  Kinases  (RTKs)

RTKs are Membrane Bound Proteins that Phosphorylate TyrosinesRTKs Play Important Roles in Regulating Cell ProliferationDimerization Important for Activity

ATP ADP

RTK

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Receptor  Tyrosine  Kinases  (RTKs)

Page 54: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Lipid Bilayer

Receptor  Tyrosine  Kinases  (RTKs)

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Lipid Bilayer

Outside of Cell

Inside of Cell (Cytoplasm)

Receptor  Tyrosine  Kinases  (RTKs)

Page 56: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Lipid Bilayer

Outside of Cell

Inside of Cell (Cytoplasm)

RTK Monomer RTK Monomer

Receptor  Tyrosine  Kinases  (RTKs)

Page 57: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Lipid Bilayer

Outside of Cell

Inside of Cell (Cytoplasm)

RTK Monomer RTK Monomer

Transmembrane α-helix

Receptor  Tyrosine  Kinases  (RTKs)

Page 58: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Lipid Bilayer

Outside of Cell

Inside of Cell (Cytoplasm)

RTK Monomer RTK Monomer

Transmembrane α-helix Cytoplasmic Tyrosine Kinase Domain

(inactive)

Receptor  Tyrosine  Kinases  (RTKs)

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Receptor  Tyrosine  Kinases  (RTKs)

Page 60: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Ligand (Hormone) Binding &

Dimerization

Receptor  Tyrosine  Kinases  (RTKs)

Page 61: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Ligand (Hormone) Binding &

Dimerization

Receptor  Tyrosine  Kinases  (RTKs)

Page 62: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Ligand (Hormone) Binding &

Dimerization

Activation of Tails Autophosphorylation

Receptor  Tyrosine  Kinases  (RTKs)

Page 63: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

Ligand (Hormone) Binding &

Dimerization

Activation of Tails Autophosphorylation P

PP P

PP

Receptor  Tyrosine  Kinases  (RTKs)

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Ligand (Hormone) Binding &

Dimerization

Activation of Tails Autophosphorylation P

PP P

PP Active Tyrosine

Kinase

Receptor  Tyrosine  Kinases  (RTKs)

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PP

PPPP

Receptor  Tyrosine  Kinases  (RTKs)

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PP

PPPP

Assembly of Signaling Complex

Receptor  Tyrosine  Kinases  (RTKs)

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PP

PPPP

Assembly of Signaling Complex

Receptor  Tyrosine  Kinases  (RTKs)

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PP

PPPP P

PPP

PP

Assembly of Signaling Complex

Receptor  Tyrosine  Kinases  (RTKs)

Page 69: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

PP

PPPP P

PPP

PP

Assembly of Signaling Complex

SH2 Domains of Proteins Recognize and Bind Phosphotyrosines

Receptor  Tyrosine  Kinases  (RTKs)

Page 70: Hormones and Signal Transduction IIoregonstate.edu/instruct/bb450/450material/Keynotes/19SignalingII.… · Receptor(Tyrosine(Kinases((RTKs) RTKs are Membrane Bound Proteins that

PP

PPPP P

PPP

PP

Assembly of Signaling Complex

Signaling Complex Communicates Message to

Cell (usually by phosphorylation)

SH2 Domains of Proteins Recognize and Bind Phosphotyrosines

Receptor  Tyrosine  Kinases  (RTKs)

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• RTK Signaling OverviewReceptor  Tyrosine  Kinases  (RTKs)

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• RTK Signaling Overview

Binding of Hormone to RTK in Membrane

Receptor  Tyrosine  Kinases  (RTKs)

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• RTK Signaling Overview

Binding of Hormone to RTK in Membrane

Receptor Dimerization

Receptor  Tyrosine  Kinases  (RTKs)

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• RTK Signaling Overview

Binding of Hormone to RTK in Membrane

Receptor Dimerization

Autophosphorylation

Receptor  Tyrosine  Kinases  (RTKs)

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• RTK Signaling Overview

Binding of Hormone to RTK in Membrane

Receptor Dimerization

Autophosphorylation

Signaling Complex Assembly

Receptor  Tyrosine  Kinases  (RTKs)

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• RTK Signaling Overview

Binding of Hormone to RTK in Membrane

Receptor Dimerization

Autophosphorylation

Signaling Complex Assembly

Communicate Message

to Cell

Receptor  Tyrosine  Kinases  (RTKs)

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RTKs  -­‐  Insulin  Receptor

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RTKs  -­‐  Insulin  Receptor

Unlike Other RTKs, Always a Dimer in Membrane

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RTKs  -­‐  Insulin  Receptor

Unlike Other RTKs, Always a Dimer in MembraneBinding of Insulin Activates Autophosphorylation of Tails

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RTKs  -­‐  Insulin  Receptor

Unlike Other RTKs, Always a Dimer in MembraneBinding of Insulin Activates Autophosphorylation of Tails

Binding of Insulin

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RTKs  -­‐  Insulin  Receptor

Unlike Other RTKs, Always a Dimer in MembraneBinding of Insulin Activates Autophosphorylation of Tails

Binding of Insulin

Autophos- phorylation

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RTKs  -­‐  Insulin  Receptor

Unlike Other RTKs, Always a Dimer in MembraneBinding of Insulin Activates Autophosphorylation of Tails

Binding of Insulin

Autophos- phorylation

IRS-1 Activation

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RTKs  -­‐  Insulin  Receptor

Unlike Other RTKs, Always a Dimer in MembraneBinding of Insulin Activates Autophosphorylation of Tails

Binding of Insulin

Autophos- phorylation

IRS-1 Activation

PI3 Kinase Activation

Other Signaling Pathways

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RTKs  -­‐  Insulin  Receptor

Unlike Other RTKs, Always a Dimer in MembraneBinding of Insulin Activates Autophosphorylation of Tails

Binding of Insulin

Autophos- phorylation

IRS-1 Activation

PIP3 Formation

PI3 Kinase Activation

Other Signaling Pathways

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RTKs  -­‐  Insulin  Receptor

Unlike Other RTKs, Always a Dimer in MembraneBinding of Insulin Activates Autophosphorylation of Tails

Binding of Insulin

Autophos- phorylation

IRS-1 Activation

PIP3 Formation

PDK1 Activation

PI3 Kinase Activation

Other Signaling Pathways

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RTKs  -­‐  Insulin  Receptor

Unlike Other RTKs, Always a Dimer in MembraneBinding of Insulin Activates Autophosphorylation of Tails

Binding of Insulin

Autophos- phorylation

IRS-1 Activation

PIP3 Formation

PDK1 Activation

Akt Kinase Activation

PI3 Kinase Activation

Other Signaling Pathways

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RTKs  -­‐  Insulin  Receptor

Unlike Other RTKs, Always a Dimer in MembraneBinding of Insulin Activates Autophosphorylation of Tails

Binding of Insulin

Autophos- phorylation

IRS-1 Activation

PIP3 Formation

PDK1 Activation

Akt Kinase Activation

Stimulate GLUT4

Movement to Cytoplasm

PI3 Kinase Activation

Other Signaling Pathways

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RTKs  -­‐  Insulin  Receptor

Unlike Other RTKs, Always a Dimer in MembraneBinding of Insulin Activates Autophosphorylation of Tails

Binding of Insulin

Autophos- phorylation

IRS-1 Activation

PIP3 Formation

PDK1 Activation

Akt Kinase Activation

Stimulate GLUT4

Movement to Cytoplasm

Cells Uptake Glucose

PI3 Kinase Activation

Other Signaling Pathways

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RTKs  -­‐  Insulin  Receptor

Unlike Other RTKs, Always a Dimer in MembraneBinding of Insulin Activates Autophosphorylation of Tails

Binding of Insulin

Autophos- phorylation

IRS-1 Activation

PIP3 Formation

PDK1 Activation

Akt Kinase Activation

Stimulate GLUT4

Movement to Cytoplasm

Cells Uptake Glucose

PI3 Kinase Activation

Other Signaling Pathways

Blood Glucose Levels

Fall

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RTKs  -­‐  Insulin  Receptor

Unlike Other RTKs, Always a Dimer in MembraneBinding of Insulin Activates Autophosphorylation of Tails

Binding of Insulin

Autophos- phorylation

IRS-1 Activation

PIP3 Formation

PDK1 Activation

Akt Kinase Activation

Stimulate GLUT4

Movement to Cytoplasm

Cells Uptake Glucose

PI3 Kinase Activation

Other Signaling Pathways

Blood Glucose Levels

Fall

Insulin Signaling AlsoActivates

PhosphoproteinPhosphatase

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Hormones  and  Signal  Transduction

Insulin Receptor Pathway

β- Adrenergic Pathway

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Hormones  and  Signal  Transduction

Insulin Receptor Pathway

β- Adrenergic PathwayG-Protein

Adenylate Cylase

cAMP

PKA Active

PK Active

GS Inactive

GP-a Active

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Hormones  and  Signal  Transduction

Insulin Receptor Pathway

β- Adrenergic PathwayG-Protein

Adenylate Cylase

cAMP

PKA Active

PK Active

GS Inactive

GP-a Active

Glycogen Broken Down

Blood Glucose Levels Rise

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Hormones  and  Signal  Transduction

Insulin Receptor Pathway

β- Adrenergic PathwayG-Protein

Adenylate Cylase

cAMP

PKA Active

PK Active

GS Inactive

GP-a Active

Glycogen Broken Down

Blood Glucose Levels RiseTyrosine Kinase Activation

IRS-1 Activation

PI3 Kinase Activation

PIP3 Formation

PDK1 Activation

Akt Kinase Activation

GLUT4 Moved to Cytoplasm

Phosphoprotein Phosphatase Activated

Glucose Taken Into Cell

PK, GP-a Inactive GS Active

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Hormones  and  Signal  Transduction

Insulin Receptor Pathway

β- Adrenergic PathwayG-Protein

Adenylate Cylase

cAMP

PKA Active

PK Active

GS Inactive

GP-a Active

Glycogen Broken Down

Blood Glucose Levels RiseTyrosine Kinase Activation

IRS-1 Activation

PI3 Kinase Activation

PIP3 Formation

PDK1 Activation

Akt Kinase Activation

GLUT4 Moved to Cytoplasm

Phosphoprotein Phosphatase Activated

Glucose Taken Into Cell

PK, GP-a Inactive GS Active

Blood Glucose Levels Fall

Glycogen Made

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RTKs  -­‐  Epidermal  Growth  Factor

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RTKs  -­‐  Epidermal  Growth  Factor

Receptor Tyrosine Kinase

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RTKs  -­‐  Epidermal  Growth  Factor

Receptor Tyrosine KinaseDimerizes on Binding Epidermal Growth Factor (EGF)

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RTKs  -­‐  Epidermal  Growth  Factor

Receptor Tyrosine KinaseDimerizes on Binding Epidermal Growth Factor (EGF)Involved in Growth, Proliferation and Cell Differentiation

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RTKs  -­‐  Epidermal  Growth  Factor

Receptor Tyrosine KinaseDimerizes on Binding Epidermal Growth Factor (EGF)Involved in Growth, Proliferation and Cell Differentiation

EGFR

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RTKs  -­‐  Epidermal  Growth  Factor

Receptor Tyrosine KinaseDimerizes on Binding Epidermal Growth Factor (EGF)Involved in Growth, Proliferation and Cell Differentiation

EGFR

EGF

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Epidermal Growth Factor Receptor (EGFR)RTKs  -­‐  Epidermal  Growth  Factor

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EGFR Signaling, Part 1Epidermal Growth Factor Receptor (EGFR)

RTKs  -­‐  Epidermal  Growth  Factor

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EGFR Signaling, Part 1Epidermal Growth Factor Receptor (EGFR)

EGFR Dimer

RTKs  -­‐  Epidermal  Growth  Factor

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EGFR Signaling, Part 1Epidermal Growth Factor Receptor (EGFR)

EGFR Dimer

Autophosphorylated Tyrosines in

Cytoplasmic Domain

RTKs  -­‐  Epidermal  Growth  Factor

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EGFR Signaling, Part 1Epidermal Growth Factor Receptor (EGFR)

EGFR Dimer

Autophosphorylated Tyrosines in

Cytoplasmic Domain

Signaling Complex Assembled on

Phosphotyrosines

RTKs  -­‐  Epidermal  Growth  Factor

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EGFR Signaling, Part 1Epidermal Growth Factor Receptor (EGFR)

EGFR Dimer

Autophosphorylated Tyrosines in

Cytoplasmic Domain

Signaling Complex Assembled on

Phosphotyrosines

GTP GDP

RTKs  -­‐  Epidermal  Growth  Factor

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EGFR Signaling, Part 1Epidermal Growth Factor Receptor (EGFR)

EGFR Dimer

Autophosphorylated Tyrosines in

Cytoplasmic Domain

Signaling Complex Assembled on

Phosphotyrosines

GTP GDP

GTP

RTKs  -­‐  Epidermal  Growth  Factor

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EGFR Signaling, Part 1Epidermal Growth Factor Receptor (EGFR)

EGFR Dimer

Autophosphorylated Tyrosines in

Cytoplasmic Domain

Signaling Complex Assembled on

Phosphotyrosines

GTP GDP

GTP

Prepares Cell for Division

RTKs  -­‐  Epidermal  Growth  Factor

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Metabolic  Melody

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Metabolic  Melody

In My Liver (to the tune of “And I Love Her”)

Copyright © Kevin Ahern

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In My Liver (to the tune of “And I Love Her”)

Copyright © Kevin Ahern

If I am missing meals

On busy days

That’s when my body steals

Glucose away

From my liver

It starts with glucagon

When I’m weak kneed

The hormone acts to spawn

New energy

In my liver

Bridge

The signaling

Acts rapidly

c-A-M-P’s

Fire up kinase

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In My Liver (to the tune of “And I Love Her”)

Copyright © Kevin Ahern

If I am missing meals

On busy days

That’s when my body steals

Glucose away

From my liver

It starts with glucagon

When I’m weak kneed

The hormone acts to spawn

New energy

In my liver

Bridge

The signaling

Acts rapidly

c-A-M-P’s

Fire up kinase

Phosphorylase then gets

Re-activated

So glycogen begets

Glucose phosphated

In my liver

Instrumental

Then in the last step here

A phosphatase

Makes phosphate disappear

With no delays

In my liver