chem 509 signal transduction winter 2010 lecture 2

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Chem 509 Signal Transduction Winter 2010 Lecture 2

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Page 1: Chem 509 Signal Transduction Winter 2010 Lecture 2

Chem 509Signal Transduction

Winter 2010

Lecture 2

Page 2: Chem 509 Signal Transduction Winter 2010 Lecture 2
Page 3: Chem 509 Signal Transduction Winter 2010 Lecture 2

What difference between Gs, Gq and Gi?:

1. Gs, G protein that is stimulatory and binds AC2. Gq, G protein that is stimulatory and binds PLC3. Gi, G protein that is inhibitory and binds AC.

Page 4: Chem 509 Signal Transduction Winter 2010 Lecture 2
Page 5: Chem 509 Signal Transduction Winter 2010 Lecture 2

O

H

H

O

OH

HH

OH

OH

OH HP

O

O

O-

H2C

CHOC

O

R2

H2C O C

O

R1 P-O

O-

O

P

O

O-

O-

Phosphatidylinositol

O

H

H

OH

OH

HH

OH

OHH

OH HP

O

O

O-

H2C

CHOC

O

R2

H2C O C

O

R1

Phosphatidylinositol-diphosphate

Page 6: Chem 509 Signal Transduction Winter 2010 Lecture 2

Phospholipases

Phospholipase A1-can hydrolyse the sn-1 acyl bond but can alsohydrolyse the sn-2 acyl bond. In the former case, this liberates a fatty acid and 2-acyl-glycerophospholipid.

O

H

H

O

OH

HH

OH

OH

OH HP

O

O

O-

H2C

CHOC

O

R2

H2C O C

O

R1 P-O

O-

O

P

O

O-

O-

Page 7: Chem 509 Signal Transduction Winter 2010 Lecture 2

O

H

H

O

OH

HH

OH

OH

OH HP

O

O

O-

H2C

CHOC

O

R2

H2C O C

O

R1 P-O

O-

O

P

O

O-

O-

Phospholipases

Phospholipase A 2-hydrolyses the sn-2 acyl bond. This liberates a fatty acid and a lysophospholipid (1-acyl-glycerophospholipid)

Page 8: Chem 509 Signal Transduction Winter 2010 Lecture 2

O

H

H

O

OH

HH

OH

OH

OH HP

O

O

O-

H2C

CHOC

O

R2

H2C O C

O

R1 P-O

O-

O

P

O

O-

O-

Phospholipases

Phospholipase C-hydrolizes one phosphoester bond to generate diacyglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3).

Page 9: Chem 509 Signal Transduction Winter 2010 Lecture 2

O

H

H

O

OH

HH

OH

OH

OH HP

O

O

O-

H2C

CHOC

O

R2

H2C O C

O

R1 P-O

O-

O

P

O

O-

O-

Phospholipases

Phospholipase D-will hydrolyse the other phosphoester bond to generate phosphatidic acid (amphiphilic product) and inositol 4,5 diphosphate (IP2).

Page 10: Chem 509 Signal Transduction Winter 2010 Lecture 2

PI=Phosphatidylinositol, Phosphorylated derivatives of PI are denoted as PIPx.PC=Phosphatidylcholine

PA=Phosphatidic acidLyso PC= deacylated phosphatidylcholine

Page 11: Chem 509 Signal Transduction Winter 2010 Lecture 2
Page 12: Chem 509 Signal Transduction Winter 2010 Lecture 2

Calmodulin

Page 13: Chem 509 Signal Transduction Winter 2010 Lecture 2
Page 14: Chem 509 Signal Transduction Winter 2010 Lecture 2
Page 15: Chem 509 Signal Transduction Winter 2010 Lecture 2

End of GPCR lecture story

Page 16: Chem 509 Signal Transduction Winter 2010 Lecture 2

Insulin signaling

Page 17: Chem 509 Signal Transduction Winter 2010 Lecture 2

Insulin signaling

Page 18: Chem 509 Signal Transduction Winter 2010 Lecture 2

Other Receptor Tyrosine Kinase Receptors

Page 19: Chem 509 Signal Transduction Winter 2010 Lecture 2

Cross talk (part of integration of signals)

Page 20: Chem 509 Signal Transduction Winter 2010 Lecture 2

Brief overview of cancer signaling pathways

Page 21: Chem 509 Signal Transduction Winter 2010 Lecture 2

Cell cycle

Page 22: Chem 509 Signal Transduction Winter 2010 Lecture 2
Page 23: Chem 509 Signal Transduction Winter 2010 Lecture 2
Page 24: Chem 509 Signal Transduction Winter 2010 Lecture 2