Download

Second Messengers and Signal Transduction






Advertisement
/ 27 []
Download Presentation
Comments
wyman
From:
|  
(1112) |   (0) |   (0)
Views: 230 | Added:
Rate Presentation: 0 0
Description:
Second Messengers and Signal Transduction. Tim Bloom, Ph.D. 104A Hall of Science 893-1712. Overview. Signal transduction- a concept Second messengers Characteristics Examples Benefits . Signal Transduction. Intra cellular communication Detection of extracellular event
Second Messengers and Signal Transduction

An Image/Link below is provided (as is) to

Download Policy: Content on the Website is provided to you AS IS for your information and personal use only and may not be sold or licensed nor shared on other sites. SlideServe reserves the right to change this policy at anytime. While downloading, If for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.











- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -




Second messengers and signal transduction l.jpgSlide 1

Second Messengers and Signal Transduction

Tim Bloom, Ph.D.

104A Hall of Science

893-1712

Overview l.jpgSlide 2

Overview

  • Signal transduction- a concept

  • Second messengers

    • Characteristics

    • Examples

    • Benefits

Signal transduction l.jpgSlide 3

Signal Transduction

  • Intracellular communication

    • Detection of extracellular event

    • Generation of internal change

  • Bottom line- presence of external ligand causes a change inside cell

Signaling examples l.jpgSlide 4

Ligands

Estrogen

Acetylcholine

Insulin

Epinephrine

Receptors

Transcription factor

Sodium channel

Receptor kinase

G protein-coupled receptor

Signaling Examples

Second messengers l.jpgSlide 5

Second Messengers

  • Molecules whose presence is a signal

  • Synthesized or released from storage

  • Act as intracellular ligands

  • Commonly used in G protein-coupled receptor signaling

    • Made or released by effector proteins

    • (Ligand for GPCR is 1st messenger)

Second messengers6 l.jpgSlide 6

Second Messengers

  • General characteristics

    • Low amounts in resting state

    • Regulated synthesis

    • Regulated destruction

    • Act through other proteins

Second messengers7 l.jpgSlide 7

Second Messengers

  • Cyclic nucleotides

    • cAMP

    • cGMP

  • Calcium

  • Lipid derivatives

    • IP3

    • DAG

    • Many others

Cyclic amp l.jpgSlide 8

Cyclic AMP

  • Made from ATP

  • Adenylate cyclase

    • Membrane effector

    • Needs a G-protein

  • Hydrolysis of cAMP to AMP terminates signal

Slide9 l.jpgSlide 9

cAMP

  • Regulates some ion channels as ligand

  • Regulates a kinase

    • Phosphorylates many substrates

    • Substrate determines effect seen

      • Increase glycogen breakdown

      • Decrease glycogen synthesis

      • Increase cardiac beat strength

      • Etc.

Camp system l.jpgSlide 10

cAMP System

  • Example of typical second messenger set up

    • Receptor

    • G protein

    • Effector protein

    • Second messenger

    • “2nd Messenger binding protein(s)”

    • Target(s) of ‘SMBPs”

    • Termination mechanism

Camp signaling path l.jpgSlide 11

cAMP Signaling Path

E

Gs

R

cAMP

ATP

Camp signaling path12 l.jpgSlide 12

cAMP Signaling Path

E

Gs

R

cAMP

+

ATP

PKA

Camp signaling path13 l.jpgSlide 13

PDE

-

cAMP Signaling Path

E

Gs

R

cAMP

+

ATP

PKA

Substrate-P

substrate

Cyclic gmp l.jpgSlide 14

Cyclic GMP

  • Made from GTP

  • Guanylate cyclase

    • Membrane or soluble

    • Acts as receptor

    • No G-protein involved

  • Hydrolysis of cGMP to GMP terminates signal

Slide15 l.jpgSlide 15

cGMP

  • Regulates several proteins as ligand

    • Ion channels

    • Protein kinase

  • Important in smooth muscle relaxation

  • Important in visual system

Calcium as a 2 nd messenger l.jpgSlide 16

Calcium as a 2nd Messenger

  • Low cytoplasmic Ca++ at rest

  • Channels open with voltage and/or ligands

  • Channels in PM and in “calciosome”

Calcium as a 2 nd messenger17 l.jpgSlide 17

Calcium as a 2nd Messenger

  • High cytoplasmic Ca++ when stimulated

  • Pumps move calcium out of cytoplasm

  • Pumps in PM and in “calciosome”

Calcium as a 2 nd messenger18 l.jpgSlide 18

Calcium as a 2nd Messenger

  • Many binding proteins mediate Ca++ action

  • Activated by calcium

    • Troponin C

    • Calmodulin

  • Calmodulin is multifunctional

Calmodulin l.jpgSlide 19

Calmodulin

Ca++

Ca++

Ca++

Ca++

Calmodulin20 l.jpgSlide 20

Calmodulin

Ca++

Ca++

Ca++

Ca++

Calmodulin targets l.jpgSlide 21

Calmodulin Targets

  • Adenylate cyclase (some versions)

  • Phosphodiesterase (some versions)

  • Myosin light chain kinase

  • Calmodulin-dependent kinases

  • Calcineurin (a phosphatase)

  • And so on…

Phospholipase c as effector l.jpgSlide 22

Inositol tri-phosphate

Hydrophilic

Agonist for internal calcium channel

[Ca++]i rises

Multiple effects through Ca++-binding proteins

Diacylglycerol

Hydrophobic

Targets PKC (a kinase)

PKC requires Ca++ and DAG

Mimicked by phorbol esters (tumorogenic)

Phospholipase C as Effector

Ip 3 dag signaling path l.jpgSlide 23

IP3/DAG Signaling Path

PKC

E

G

R

Substrate-P

substrate

IP3 & DAG

PI

Ca++

calciosome

Why 2 nd messengers l.jpgSlide 24

Why 2nd Messengers?

  • Complicated pathways

    • Difficult to understand

    • Hard to learn

    • Many parts makes easy to be disrupted

  • Complexity allows flexibility

    • More graded cellular responses

    • Interaction of pathways

    • Signal amplification

Signals and effects l.jpgSlide 25

Signals and Effects

  • Signal is required to produce cellular change

    • Signal generated by receptor (or effector)

    • Signal size related to # of active receptors

    • (dose response!)

Signal amplification l.jpgSlide 26

Signal Amplification

  • Example from G protein-coupled receptor

    • Activated receptor hits several G proteins

    • Each effector makes/ releases many molecules

    • 2nd messenger receptor also amplifies, especially if it’s a kinase

  • Bottom line: one molecule of extracellular ligand generates many modified proteins inside the cell ( a large signal)

Review l.jpgSlide 27

Review

  • Ligand binding alters receptor

  • Some receptors use signaling molecules

    • Synthesized from precursors

    • Released from storage site

    • Called second messengers

  • Second messengers activate other proteins

    • Activation acts as signal, changes things

    • Second messenger is removed to end signal


Copyright © 2014 SlideServe. All rights reserved | Powered By DigitalOfficePro