ADRENERGIC RECEPTORS Extracellular S N S S T Q N P G T F N A D - - PowerPoint PPT Presentation

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ADRENERGIC RECEPTORS Extracellular S N S S T Q N P G T F N A D - - PowerPoint PPT Presentation

Mar 09, 2024 617 likes •876 views

1B 1B -Adrenoceptor phosphorylation. Adrenoceptor phosphorylation. Roles(s) of autocrine/ paracrine Roles(s) of autocrine/ paracrine Communication? Communication? J. Adolfo Garca J. Adolfo Garca- -Sinz Sinz Instituto de

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SLIDE 1

α1B

1B-Adrenoceptor phosphorylation.

Adrenoceptor phosphorylation. Roles(s) of autocrine/ paracrine Roles(s) of autocrine/ paracrine Communication? Communication?

  • J. Adolfo García
  • J. Adolfo García-
  • Sáinz

Sáinz Instituto de Fisiología Celula Instituto de Fisiología Celula UNAM UNAM

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SLIDE 2

ADRENERGIC RECEPTORS

α

1

α2 β β3 β1 β2 α1A α1D α1B α2C α2A α2B

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SLIDE 3

N P G T T Q A D K L F N W Q A P E G T N H G A S L D P N T D M S N S S S V G T L P Q L D V T R A I V L G A I L F F A V N L G V I S L V L I I V E L A S F P V T L F S L D I L A L V N I T L A A C N R H L R T P T N Y F L G Y W V L G R I F C D I W A V D V C C L T A I S C L A I I S A S L E K W L L P G I V T L W S V L L L A I G S V A

D R Y

I G V R Y S L Q Y P T L V R R K T P A N D D K E T E E G P F Y L F S S G S L F Y P A I L L V Y M C A I V P A G V M L E K N S R

T T K N V Y I VA R

E M S

N K S H F L T L E I R K

ED I S A V F V V F W G Y L F N C N I L I Y C S K S P C V S S T K T L G H N P A K S I A R S K V K L F FS

R E K K A A K

T L S G P L I F P F L W L F G I V V G L L C M I A F S T L K P P D P S K E F K R A F M R I L G C Q C R S S R E L

S Q

G R T W

S

G Y T Y A P R G L R R C A R R R R R R G

S

D K R C M S G GS R T L P S Q S P S P S A L G R G G Y P P L E A Q L L D D S C A T F L P K F D L R G G S G P P E R R S L L A P L K W E P G S Y E G L L G D A S T E G C D A N G D L A N T T P G F K G Q M P S N S L P G P E A P G H F

Plasma membrane Extracellular Intracellular

Phosphorylation sites PKC S GRK S D142 A or T Constitutive activity Gα14 coupling sites A293 E or I Constitutive activity Amino-terminus Carboxyl-terminus Gαq coupling site

H

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SLIDE 4
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SLIDE 5

1 2 3 4 5

25 50 75 100

EFFECT

[DRUG]

Desensitization Desensitization

slide-6
SLIDE 6

Homologous desensitization Homologous desensitization

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SLIDE 7

PI3K PDK-1 ? PKC

Agonist Agonist

PL-C DG

Heterologous desensitization Heterologous desensitization

slide-8
SLIDE 8

Does LPA induce Does LPA induce

α1B

1B-AR phosphorylation?

AR phosphorylation? How does it take place? How does it take place?

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SLIDE 9

PI3K

LPA-R

Gi

γβ

γ

α AC AMPc

ions

IP3 DG PLC

slide-10
SLIDE 10

100 150 200 250

  • 10
  • 8
  • 6
  • 4
  • 10 - 9 - 8 - 7 - 6 - 5

LOG [ LPA ] M LOG [ LPA ] M

α1b-AR PHOSPHORYLATION (% OF BASAL)

NE LPA TPA CONTROL PT X 100 200 300

B NE LPA TPA PTX μ g/ml

0.0 0.3

*

α 1b-AR PHOSPHORYLATION (% OF BASAL)

CONT STAU GEN WORT NE LP A 100 200 300

* *

α1b-AR PHOSPHORYLATION (% OF BASAL)

W OR T C ONT GEN STAU B L PA NE

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SLIDE 11

α1B-AR

?

? PI3K

LPA-R

Gi PKC

γβ

γ

α PDK1

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SLIDE 12
slide-13
SLIDE 13
slide-14
SLIDE 14
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SLIDE 15

α1B-AR LPA-R

Gi PKC

γβ

γ

α PDK PI3K EGF-R MP HB-EGF

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SLIDE 16

Is the EFG receptor role general ? Is the EFG receptor role general ?

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SLIDE 17

100 125 150 175

α1B-Adrenoceptor Phosphorylation (% of basal)

  • Log [Noradrenaline] M

NA NA +AG B

  • 9
  • 8
  • 5
  • 9
  • 7
  • 5
  • 7
  • 6

100 125 150 175 200 225

  • Log [Endothelin-1] M

B Et-1 Et-1 +AG

  • 7
  • 9
  • 10
  • 10 -9
  • 8
  • 7
  • 8

α1B-Adrenoceptor Phosphorylation (% of basal)

100 150 200 250

  • Log [PMA] M

PMA PMA +AG B

  • 9
  • 7
  • 6
  • 9
  • 8
  • 7
  • 6
  • 8

α1B-Adrenoceptor Phosphorylation (% of basal)

slide-18
SLIDE 18

Basal Et-1 +AG +BB +aHB-EGF +WT

100 150 200 Basal Et +BB +aHB-EGF +AG +WT

* ** ** ** **

α1B-Adrenoceptor Phosphorylation

(% of basal)

EGF receptor autophosphorylation Basal Et Et + BB-94 EGF EGF + BB -94

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SLIDE 19

Basal NA +AG +BB +aHB-EGF +WT

100 150 200 Basal NA +BB +aHB-EGF +AG

* ** ** **

α1B-Adrenoceptor Phosphorylation (% of basal)

+WT

EGF receptor autophosphorylation Basal Basal + BB-94 NA NA + BB-94 EGF EGF + BB-94

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SLIDE 20

α1B-AR

γβ

γ

α GRK MP

EGF-R

PI3K PDK PKC

HB-EGF

DG

Model for Model for α1B

1B-AR homologous desensitization

AR homologous desensitization

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SLIDE 21

Does TRK activation induce Does TRK activation induce

α1D

1D-AR phosphorylation and

AR phosphorylation and desensitization? desensitization?

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SLIDE 22

25 50 75 100 1000 2000 NA Time (seconds) Δ[Ca2+]i [nM] 25 50 75 100 1000 2000 NA + INS Time (seconds) Δ[Ca2+]i [nM] 25 50 75 100 1000 2000 NA + IGF-I Time (seconds) Δ[Ca2+]i [nM] 25 50 75 100 1000 2000 NA + EGF Time (seconds) Δ[Ca2+]i [nM] 25 50 75 100 1000 2000 NA + PDGF Time (seconds) Δ[Ca2+]i [nM]

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SLIDE 23

100 150 200 250

α1D-Adrenoceptor phosphorylation ( % of basal)

0 0.01 1.0 100

Insulin (ng/ml)

0 0.01 0.1 1.0 10 100 100 150 200 250

α1D-Adrenoceptor phosphorylation ( % of basal)

IGF- I 0 1 3 10 30 100 0 1 10 100

IGF -I (ng/ml)

100 150 200 250

α1D-Adrenoceptor phosphorylation ( % of basal)

0 0.01 1.0 100 0 0.01 0.1 1.0 10 100

EGF (ng/ml)

100 150 200 250

α1D-Adrenoceptor phosphorylation ( % of basal)

0 0.01 1.0 100

PDGF (ng/ml)

0 0.01 0.1 1.0 10 100

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SLIDE 24

Patricia Casas Patricia Casas-

  • González

González

  • M. Teresa Romero
  • M. Teresa Romero-
  • Ávila

Ávila Tzindilú Molina Tzindilú Molina-

  • Muñoz

Muñoz Ekaterina Rodríguez Ekaterina Rodríguez Ekaterina Kalashnikova Ekaterina Kalashnikova Erika Calvo Erika Calvo Guadalupe Reyes Guadalupe Reyes-

  • Cruz

Cruz-

  • CINVESTAV

CINVESTAV