Difference between revisions of "Signal 1"

From CellBiology
 
(78 intermediate revisions by 2 users not shown)
Line 1: Line 1:
{{Template:Lecture Header}}
+
=Cell Signaling 1=
  
=Cell Signaling 1=
+
This lecture is an introduction to a series of lectures on cell signaling. The first lecture is a general introduction to the different signaling mechanisms and second messengers. The lecture will also describe the  signaling pathways through cytoplasmic and nuclear steroid signaling pathway. The following lecture (2) looks in detail at some specific examples of signaling pathways through membrane receptors.
 +
 
 +
Note that you have already been introduced to signaling in many of your other lecture topics.
 +
 
 +
 
 +
'''Lecture Slides:''' [[Media:2017 Signal 1.pdf|'''2017 Lecture PDF''']] | [[Media:2017 Signal 1-4.pdf|'''2017 Lecture PDF 4 slides/page''']]
 +
 
 +
 
 +
Note - The information shown on this page below is for background purposes only, the slides linked above will be used in this lecture presentation.
  
This lecture is an introduction to a series of lectures on cell signaling. The first lecture is a general introduction to the different signaling mechanisms and the following two lectures look in detail at some specific examples of signaling pathways. 
 
  
Note that you have already been introduced to signaling in many of your other lecture topics (searching PubMed for "cell signaling" gives 410,092 results).
 
  
'''2009''' [[2009_Lecture_19|lecture]] '''2008''': [http://cellbiology.med.unsw.edu.au/units/science/lecture0818.htm ANAT3231 Lecture 18-19 Cell Signaling]
+
'''Archive:''' [https://cellbiology.med.unsw.edu.au/cellbiology/index.php?title=Signal_1&oldid=77604 2016] | [https://cellbiology.med.unsw.edu.au/cellbiology/index.php?title=Signal_1&oldid=67060 2015] | [http://php.med.unsw.edu.au/cellbiology/index.php?title=Signal_1&oldid=46351 2013] | [[2010_Lecture_19|2010 lecture]] | [[2009_Lecture_19|2009 lecture]]  
  
 
[[File:Cells.jpg|300px]]
 
[[File:Cells.jpg|300px]]
Line 32: Line 38:
 
==Signaling Mechanisms==
 
==Signaling Mechanisms==
  
[http://www.ncbi.nlm.nih.gov:80/books/bookres.fcgi/mcb/ch20anim2.mov MCB Movie - Extracellular Signaling]
+
[http://www.ncbi.nlm.nih.gov/books/NBK2151  MCB - Extracellular Signaling]
* Endocrine
+
{|
** Hormone (at a distance)
+
|
* Paracrine
+
* '''Endocrine''' - Hormone (at a distance)
** Locally
+
* '''Paracrine''' - Locally
* Neurotransmitter  
+
** Neurotransmitter - Specific form of paracrine
** Specific form of paracrine
+
* '''Autocrine''' - Local (self)
* Autocrine
+
** Contact Dependent
* Local (self)
+
| [[File:Signal_transduction_pathways.png|500px]]
* Contact Dependent
+
|}
 
 
[[File:Signal_transduction_pathways.png|600px]]
 
  
* [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=cooper.section.2199#2200 Cell - Modes of Cell-Cell Signaling] | [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mcb.chapter.5687  MCB - Cell-to-Cell Signaling: Hormones and Receptors] |  [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mcb.section.5717  MCB - Overview of Extracellular Signaling] | [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=cooper.chapter.2198 Cell - Cell Signaling]
 
  
* [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mboc4.chapter.2740 MCoB - Cell Communication] | [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mboc4.section.2743 MCoB - General Principles of Cell Communication]  
+
:'''Links:''' [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=cooper.section.2199#2200 Cell - Modes of Cell-Cell Signaling] | [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mcb.chapter.5687  MCB - Cell-to-Cell Signaling: Hormones and Receptors] |  [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mcb.section.5717  MCB - Overview of Extracellular Signaling] | [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=cooper.chapter.2198 Cell - Cell Signaling] | [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mboc4.chapter.2740 MCoB - Cell Communication] | [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mboc4.section.2743 MCoB - General Principles of Cell Communication] | [http://www.cellsignal.com/reference/pathway/Adherens_Junction.html Adherens Junction Dynamics] | [http://www.cellsignal.com/pathways/ Commercial Database - Pathways]
* Adhesion - [http://www.cellsignal.com/reference/pathway/Adherens_Junction.html Adherens Junction Dynamics]
 
  
 
==Cell Communication==
 
==Cell Communication==
* Contact Mediated
+
* '''Contact Mediated''' - display molecules on cell surface, recognized by receptor on another cell
** display molecules on cell surface
+
* '''Non-Contact Mediated''' - chemical signal, nearby or at a distance
** recognized by receptor on another cell
+
* Common Signals Signals and Receptors
* Non-Contact Mediated
 
** chemical signal
 
** nearby or at a distance
 
 
 
Common Signals
 
Signals and Receptors
 
Signal Transduction Model
 
Signaling between Tissues
 
Regulation of cells and tissues
 
 
 
Hormones
 
secreted by one tissue to regulate function of other cells or tissues
 
  
 
==Chemical Signal Types==
 
==Chemical Signal Types==
Line 74: Line 64:
  
 
==Extracellular Signal Steps==
 
==Extracellular Signal Steps==
* Signaling Molecule
+
Signaling Molecule
* Synthesis
+
# Synthesis
* Release by signaling cell
+
# Release by signaling cell
* Transport to target cell
+
# Transport to target cell
* Detection by a specific receptor protein
+
# Detection by a specific receptor protein
*Change by receptor-signal complex (trigger)
+
# Change by receptor-signal complex (trigger)
 +
 
 +
There can also be a feedback mechanism following signaling.
  
 
==Cell Surface Receptors==
 
==Cell Surface Receptors==
Line 94: Line 86:
  
 
==Second Messengers==
 
==Second Messengers==
[[Image:Cyclic-adenosine-monophosphate-2D-skeletal.png|thumb|cAMP molecular structure]]
+
{|
[[Image:Cyclic guanosine monophosphate.png|thumb|Cyclic guanosine monophosphate (cGMP)]]
+
| [[Image:Cyclic-adenosine-monophosphate-2D-skeletal.png|200px]]
* Cyclic nucleotides
+
 
** cAMP, cGMP
+
Cyclic  adenosine monophosphate (cAMP)
 +
| [[Image:Cyclic guanosine monophosphate.png|200px]]
 +
 
 +
Cyclic guanosine monophosphate (cGMP)
 +
|}
 +
 
 +
* Cyclic nucleotides - cAMP, cGMP (will cover also in next lecture G protein signalling)
 
* Calcium Ions
 
* Calcium Ions
* Protein Kinase A
+
* Inositol 1,4,5-trisphosphate (IP3) (see also IP3 receptor PMID 9243320) IP3 receptor plays in the conversion of numerous external stimuli to intracellular Ca2+ signal
** PKA, B, C
+
* Diacylglycerol (DAG) - modified lipid activates PKC
* diacylglycerol (DAG)
+
* Protein Kinase A - PKA, B, C (phosphorylate other proteins)
** modified lipid activates PKC
+
* regulate the activity of cellular proteins (enzymes and non-enzymatic)
* regulate the activity of cellular proteins
 
** enzymes and non-enzymatic
 
  
'''Links:''' [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?rid=mcb.figgrp.5737 Cell - Common intracellular signaling proteins] [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mcb&part=A5853&rendertype=figure&id=A5867 Elevation of cytosolic Ca2+ via the inositol-lipid signaling pathway] | [http://www.ncbi.nlm.nih.gov/bookshelf/picrender.fcgi?book=mcb&part=A5717&blobname=ch20anim1.mov View Movie: Second Messengers in Signaling Pathways]
+
'''Links:''' [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?rid=mcb.figgrp.5737 Cell - Common intracellular signaling proteins] [http://www.ncbi.nlm.nih.gov/books/NBK21517/figure/A5737 Elevation of cytosolic Ca2+ via the inositol-lipid signaling pathway] | [http://www.ncbi.nlm.nih.gov/books/NBK21517/figure/A5733 Movie: Second Messengers in Signaling Pathways]
  
 
==Steroid Responses==
 
==Steroid Responses==
 
[[Image:Steroid hormone receptor signaling.gif|thumb|Steroid hormone receptor signaling]]
 
[[Image:Steroid hormone receptor signaling.gif|thumb|Steroid hormone receptor signaling]]
 
[[Image:Steroidogenesis.png|thumb|Steroidogenesis]]
 
[[Image:Steroidogenesis.png|thumb|Steroidogenesis]]
* Intracellular Receptors
+
{|
* Steroid Hormones  
+
|
 +
* Intracellular Receptors (longest acting of hormone classes, hours-days)
 +
* Steroid Hormones (androgens, glucocorticoids, mineralocorticoids)
 
** [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=mcb.section.5717#5746  MCB - Steroid Hormones, Thyroxine, and Retinoic Acid] | [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cooper.figgrp.2203 Cell - Structure of steroid hormones, thyroid hormone, vitamin D 3, and retinoic acid]
 
** [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=mcb.section.5717#5746  MCB - Steroid Hormones, Thyroxine, and Retinoic Acid] | [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cooper.figgrp.2203 Cell - Structure of steroid hormones, thyroid hormone, vitamin D 3, and retinoic acid]
** thyroxine
+
** thyroxine (thyroid, not a steroid)
 
** vitamin D3
 
** vitamin D3
 
** retinoic acid
 
** retinoic acid
** estrogens and testosterone (derivatives of cholesterol)
+
** cortisol (adrenal)
 +
** estrogens and testosterone (gonad)
 +
* All steroid hormones are synthesized from cholesterol.
 +
* Steroid hormones are less soluble in aqueous solution, most in blood as complexes bound to specific plasma globulins or albumin (synthesised in the liver)
 +
| [[File:Hypothalamus_endocrine_system.jpg|300px]]
  
 +
|}
 
[[Media:Steroid_signaling_cartoon.mov|Steroid_signaling_cartoon]]
 
[[Media:Steroid_signaling_cartoon.mov|Steroid_signaling_cartoon]]
  
 +
===Other Endocrine Axes===
 +
<gallery>
 +
File:HPA_axis.jpg|Hypothalamus - Pituitary - Adrenal
 +
File:HPT axis.jpg|Hypothalamus - Pituitary - Thyroid
 +
File:HPG female axis.jpg|Hypothalamus - Pituitary - Gonad (female)
 +
File:HPG male axis.jpg|Hypothalamus - Pituitary - Gonad (male)
 +
</gallery>
 +
 +
 +
[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mcb.table.5744  MCB - Characteristic Properties of Principal Types of Mammalian Hormones] | [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=mboc4.figgrp.2763 MCoB - Some signaling molecules that bind to nuclear receptors]  | [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cooper.figgrp.2204 Cell - Action of steroid hormones]
  
Cytosol location
+
==Steroid Hormone Receptors (SHRs)==
 +
[[Image:Steroid hormone receptor signaling.gif|thumb|Steroid hormone receptor signaling]]
 +
'''Cytosol location'''
 
* receptor bound to inhibitor
 
* receptor bound to inhibitor
 
* ligand binding activates receptor
 
* ligand binding activates receptor
 
* translocates to nucleus on ligand binding
 
* translocates to nucleus on ligand binding
Nuclear location
+
'''Nuclear location'''
 
* binds ligand and DNA
 
* binds ligand and DNA
 
* becomes '''transcription factor'''
 
* becomes '''transcription factor'''
  
[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mcb.table.5744  MCB - Characteristic Properties of Principal Types of Mammalian Hormones] | [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=mboc4.figgrp.2763 MCoB - Some signaling molecules that bind to nuclear receptors]  | [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cooper.figgrp.2204 Cell - Action of steroid hormones]
 
 
==Steroid Hormone Receptors (SHRs)==
 
48 human nuclear receptor types
 
 
[[Image:Steroid hormone receptor family.gif|thumb|Steroid hormone receptor family]]
 
 
* estrogen receptor, two forms ERα [NR3A1] and ERβ [NR3A2]
 
* estrogen receptor, two forms ERα [NR3A1] and ERβ [NR3A2]
 
* cortisol binding glucocorticoid receptor (GR) [NR3C1]
 
* cortisol binding glucocorticoid receptor (GR) [NR3C1]
Line 146: Line 155:
 
[http://www.cellsignal.com/pathways/nuclear-receptor.jsp Nuclear Receptor Signaling]
 
[http://www.cellsignal.com/pathways/nuclear-receptor.jsp Nuclear Receptor Signaling]
  
==Steroid Receptors==
+
===Receptor Structure===
* steroid binding region
+
[[File:Nuclear_receptor_cartoon_01.jpg|thumb|Nuclear Receptor]]
* near C-terminus
+
* '''steroid binding region''' - near C-terminus
* DNA binding
+
* '''DNA binding''' - central region
* central region
+
** zinc finger motif
* zinc finger motif
+
** alpha helix and 2 beta sheets held in place by cysteine or histidine residues by a zinc atom
* alpha helix and 2 beta sheets held in place by cysteine or histidine residues by a zinc atom
+
** multiple fingers typical
* multiple fingers typical
 
 
* DNA response element
 
* DNA response element
 
* Enhancer
 
* Enhancer
  
=== Types ===
+
:'''Links:''' [http://www.ncbi.nlm.nih.gov/books/NBK20/box/A31 Box 1.12Steroid receptors, zinc fingers and DNA binding]
 
+
=== Receptor Types ===
 +
48 human nuclear receptor types
 +
[[Image:Steroid hormone receptor family.gif|thumb|Steroid hormone receptor family]]
 
* '''Type I Receptors'''
 
* '''Type I Receptors'''
 
** Sex hormone receptors (sex hormones) - Androgen receptor, Estrogen receptor, Progesterone receptor
 
** Sex hormone receptors (sex hormones) - Androgen receptor, Estrogen receptor, Progesterone receptor
Line 169: Line 179:
 
** Thyroid hormone receptor
 
** Thyroid hormone receptor
 
* '''Orphan receptors'''
 
* '''Orphan receptors'''
 +
 +
:'''Links:''' [http://www.nature.com/nri/journal/v6/n1/fig_tab/nri1748_F2.html nuclear-receptor superfamily three classes] | [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995128/figure/Fig1/ Image - Models of sex steroid action in target tissue]
  
 
==Eicosanoids==
 
==Eicosanoids==
 +
* (icosanoids) prostaglandins, prostacyclins, thromboxanes and leukotrienes
 
* lipids acting as signaling molecules  
 
* lipids acting as signaling molecules  
* act by binding to cell surface receptors
+
**  made from essential fatty acids (EFAs) oxidation (arachidonic acid)
** prostaglandins, prostacyclin, thromboxanes, and leukotrienes
+
* act by binding to cell surface receptors, rapidly broken down (anti-inflammatory drugs act by downregulating eicosanoid synthesis)
* rapidly broken down  
 
 
* act locally in autocrine or paracrine signaling pathways
 
* act locally in autocrine or paracrine signaling pathways
* synthesized from arachidonic acid
+
 
 +
 
 +
:'''Links:''' [http://www.dkfz.de/en/f020/groups/krieg/pics/figure_1.jpg Eicosanoid biosynthesis cartoon] | [https://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb2/part1/prostag.htm Prostaglandins]
 +
 
 +
==Nitric Oxide==
 +
* (nitrogen monoxide) another signaling method that crosses lipid membranes
 +
* simple gas, very quick short-lived signal
 +
** synthesised from arginine by nitric oxide synthase
 +
* does not bind intracellular receptor
 +
** regulates intracellular enzymes
 +
 
 +
Example - dilation of blood vessels. (nitroglycerine for heart converted to NO)
  
 
== References ==
 
== References ==
Line 231: Line 254:
  
 
* "cell signaling"  [http://www.ncbi.nlm.nih.gov/sites/gquery?itool=toolbar&cmd=search&term=cell+signaling Entrez all databases]
 
* "cell signaling"  [http://www.ncbi.nlm.nih.gov/sites/gquery?itool=toolbar&cmd=search&term=cell+signaling Entrez all databases]
* "steroid signaling"  [http://www.ncbi.nlm.nih.gov/sites/gquery?itool=toolbar&cmd=search&term=steroid+signaling Entrez all databases]
+
* "steroid signaling"  [http://www.ncbi.nlm.nih.gov/sites/gquery?itool=toolbar&cmd=search&term=steroid+signaling Entrez all databases] | [http://www.ncbi.nlm.nih.gov/images?term=steroid%20signaling images]
  
 
====Reviews====
 
====Reviews====
 
+
<pubmed>23838532</pubmed>
 
<pubmed>21346732</pubmed>
 
<pubmed>21346732</pubmed>
 
<pubmed>18396093</pubmed>| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18396093 PMC]  
 
<pubmed>18396093</pubmed>| [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18396093 PMC]  
Line 244: Line 267:
  
 
==External Links==
 
==External Links==
 +
{{External Links}}
  
 
* [http://www.signaling-gateway.org/molecule/ Nature Signaling Gateway]
 
* [http://www.signaling-gateway.org/molecule/ Nature Signaling Gateway]
Line 249: Line 273:
 
* [http://www.nursa.org/flash/gene/nuclearreceptor/start.html NURSA - Nuclear Receptor Signaling: Concepts and Models]
 
* [http://www.nursa.org/flash/gene/nuclearreceptor/start.html NURSA - Nuclear Receptor Signaling: Concepts and Models]
 
* [http://www.cellsignal.com/index.jsp Cell Signaling Technology] - [http://www.cellsignal.com/pathways/chromatin.jsp Chromatin/Epigenetics] | [http://www.cellsignal.com/pathways/map-kinase.jsp MAPK Signaling] | [http://www.cellsignal.com/pathways/apoptosis-signaling.jsp Apoptosis/Autophagy] | [http://www.cellsignal.com/pathways/akt-signaling.jsp PI3K/Akt Signaling] | [http://www.cellsignal.com/pathways/translational-control.jsp Translational Control] | [http://www.cellsignal.com/pathways/ca-camp-lipid-signaling.jsp Ca, cAMP &amp; Lipid Signaling] | [http://www.cellsignal.com/pathways/cell-cycle.jsp Cell Cycle/Checkpoint] | [http://www.cellsignal.com/pathways/dna-damage.jsp DNA Damage] | [http://www.cellsignal.com/pathways/jak-stat.jsp Jak/Stat Pathway] | [http://www.cellsignal.com/pathways/nk-kappab-signaling.jsp NF-κB Signaling] | [http://www.cellsignal.com/pathways/tgf-beta-smad.jsp TGF-β/Smad Signaling] | [http://www.cellsignal.com/pathways/lymphocyte.jsp Lymphocyte Signaling] | [http://www.cellsignal.com/pathways/neuroscience.jsp Neuroscience] | [http://www.cellsignal.com/pathways/angiogenesis.jsp Angiogenesis] | [http://www.cellsignal.com/pathways/vesicle-trafficking.html Vesicle Trafficking] | [http://www.cellsignal.com/pathways/cytoskeletal.jsp Cytoskeletal Signaling] | [http://www.cellsignal.com/pathways/adhesion.jsp Adhesion] | [http://www.cellsignal.com/pathways/glucose-metabolism.jsp Glucose Metabolism] | [http://www.cellsignal.com/pathways/wnt-hedgehog.jsp Wnt/Hedgehog/Notch] | [http://www.cellsignal.com/pathways/protein-folding.jsp Protein Folding] | [http://www.cellsignal.com/pathways/protein-stability.jsp Protein Stability]
 
* [http://www.cellsignal.com/index.jsp Cell Signaling Technology] - [http://www.cellsignal.com/pathways/chromatin.jsp Chromatin/Epigenetics] | [http://www.cellsignal.com/pathways/map-kinase.jsp MAPK Signaling] | [http://www.cellsignal.com/pathways/apoptosis-signaling.jsp Apoptosis/Autophagy] | [http://www.cellsignal.com/pathways/akt-signaling.jsp PI3K/Akt Signaling] | [http://www.cellsignal.com/pathways/translational-control.jsp Translational Control] | [http://www.cellsignal.com/pathways/ca-camp-lipid-signaling.jsp Ca, cAMP &amp; Lipid Signaling] | [http://www.cellsignal.com/pathways/cell-cycle.jsp Cell Cycle/Checkpoint] | [http://www.cellsignal.com/pathways/dna-damage.jsp DNA Damage] | [http://www.cellsignal.com/pathways/jak-stat.jsp Jak/Stat Pathway] | [http://www.cellsignal.com/pathways/nk-kappab-signaling.jsp NF-κB Signaling] | [http://www.cellsignal.com/pathways/tgf-beta-smad.jsp TGF-β/Smad Signaling] | [http://www.cellsignal.com/pathways/lymphocyte.jsp Lymphocyte Signaling] | [http://www.cellsignal.com/pathways/neuroscience.jsp Neuroscience] | [http://www.cellsignal.com/pathways/angiogenesis.jsp Angiogenesis] | [http://www.cellsignal.com/pathways/vesicle-trafficking.html Vesicle Trafficking] | [http://www.cellsignal.com/pathways/cytoskeletal.jsp Cytoskeletal Signaling] | [http://www.cellsignal.com/pathways/adhesion.jsp Adhesion] | [http://www.cellsignal.com/pathways/glucose-metabolism.jsp Glucose Metabolism] | [http://www.cellsignal.com/pathways/wnt-hedgehog.jsp Wnt/Hedgehog/Notch] | [http://www.cellsignal.com/pathways/protein-folding.jsp Protein Folding] | [http://www.cellsignal.com/pathways/protein-stability.jsp Protein Stability]
 +
*  [http://www.abcam.com/index.html?pageconfig=productmap&cl=2105 Abcam signaling tools]
  
  
  
{{Template:2011ANAT3231}}
+
{{2017ANAT3231}}

Latest revision as of 13:18, 16 May 2017

Cell Signaling 1

This lecture is an introduction to a series of lectures on cell signaling. The first lecture is a general introduction to the different signaling mechanisms and second messengers. The lecture will also describe the signaling pathways through cytoplasmic and nuclear steroid signaling pathway. The following lecture (2) looks in detail at some specific examples of signaling pathways through membrane receptors.

Note that you have already been introduced to signaling in many of your other lecture topics.


Lecture Slides: 2017 Lecture PDF | 2017 Lecture PDF 4 slides/page


Note - The information shown on this page below is for background purposes only, the slides linked above will be used in this lecture presentation.


Archive: 2016 | 2015 | 2013 | 2010 lecture | 2009 lecture

Cells.jpg

Movie - Neutrophil chasing Bacterium

Objectives

  • Understand main types of signaling mechanisms
  • Understand concept of receptor and ligand
  • Understand membrane, cytoplasmic and nuclear receptors
  • Brief understanding of steroid hormone pathway
  • Brief understanding protein growth factor pathway
  • Understand differences between select membrane receptors (G protein structure, tyrosine kinases)

Lecture Summary

  • Messengers and Receptors
  • chemical signals
  • cellular receptors
  • signal transduction
  • intracellular pathways
  • second messengers
  • Examples of signaling

Signaling Mechanisms

MCB - Extracellular Signaling

  • Endocrine - Hormone (at a distance)
  • Paracrine - Locally
    • Neurotransmitter - Specific form of paracrine
  • Autocrine - Local (self)
    • Contact Dependent
Signal transduction pathways.png


Links: Cell - Modes of Cell-Cell Signaling | MCB - Cell-to-Cell Signaling: Hormones and Receptors | MCB - Overview of Extracellular Signaling | Cell - Cell Signaling | MCoB - Cell Communication | MCoB - General Principles of Cell Communication | Adherens Junction Dynamics | Commercial Database - Pathways

Cell Communication

  • Contact Mediated - display molecules on cell surface, recognized by receptor on another cell
  • Non-Contact Mediated - chemical signal, nearby or at a distance
  • Common Signals Signals and Receptors

Chemical Signal Types

  • water soluble
  • lipid soluble

Movie: Hormone Signaling

Extracellular Signal Steps

Signaling Molecule

  1. Synthesis
  2. Release by signaling cell
  3. Transport to target cell
  4. Detection by a specific receptor protein
  5. Change by receptor-signal complex (trigger)

There can also be a feedback mechanism following signaling.

Cell Surface Receptors

  • four main classes
    • G protein–coupled receptors
    • ion-channel receptors
    • receptors linked to cytosolic tyrosine kinases
    • receptors with intrinsic catalytic activity
  • ligand binding to cell-surface receptor
    • trigger intracellular pathways
    • modulate cellular metabolism, function, or development
  • Removal of the signal
    • often terminates cellular response

Second Messengers

Cyclic-adenosine-monophosphate-2D-skeletal.png

Cyclic adenosine monophosphate (cAMP)

Cyclic guanosine monophosphate.png

Cyclic guanosine monophosphate (cGMP)

  • Cyclic nucleotides - cAMP, cGMP (will cover also in next lecture G protein signalling)
  • Calcium Ions
  • Inositol 1,4,5-trisphosphate (IP3) (see also IP3 receptor PMID 9243320) IP3 receptor plays in the conversion of numerous external stimuli to intracellular Ca2+ signal
  • Diacylglycerol (DAG) - modified lipid activates PKC
  • Protein Kinase A - PKA, B, C (phosphorylate other proteins)
  • regulate the activity of cellular proteins (enzymes and non-enzymatic)

Links: Cell - Common intracellular signaling proteins Elevation of cytosolic Ca2+ via the inositol-lipid signaling pathway | Movie: Second Messengers in Signaling Pathways

Steroid Responses

Steroid hormone receptor signaling
Steroidogenesis
Hypothalamus endocrine system.jpg

Steroid_signaling_cartoon

Other Endocrine Axes


MCB - Characteristic Properties of Principal Types of Mammalian Hormones | MCoB - Some signaling molecules that bind to nuclear receptors | Cell - Action of steroid hormones

Steroid Hormone Receptors (SHRs)

Steroid hormone receptor signaling

Cytosol location

  • receptor bound to inhibitor
  • ligand binding activates receptor
  • translocates to nucleus on ligand binding

Nuclear location

  • binds ligand and DNA
  • becomes transcription factor
  • estrogen receptor, two forms ERα [NR3A1] and ERβ [NR3A2]
  • cortisol binding glucocorticoid receptor (GR) [NR3C1]
  • aldosterone binding mineralocorticoid receptor (MR) [NR3C2]
  • progesterone receptor (PR) [NR3C3]
  • dihydrotestosterone (DHT) binding androgen receptor (AR) [NR3C4]

Steroid_signaling_cartoon

Nuclear Receptor Signaling

Receptor Structure

Nuclear Receptor
  • steroid binding region - near C-terminus
  • DNA binding - central region
    • zinc finger motif
    • alpha helix and 2 beta sheets held in place by cysteine or histidine residues by a zinc atom
    • multiple fingers typical
  • DNA response element
  • Enhancer
Links: Box 1.12Steroid receptors, zinc fingers and DNA binding

Receptor Types

48 human nuclear receptor types

Steroid hormone receptor family
  • Type I Receptors
    • Sex hormone receptors (sex hormones) - Androgen receptor, Estrogen receptor, Progesterone receptor
    • Glucocorticoid receptor (glucocorticoids)
    • Mineralocorticoid receptor (mineralocorticoids)
  • Type II Receptors
    • Vitamin A receptor
    • Vitamin D receptor
    • Retinoid receptor
    • Thyroid hormone receptor
  • Orphan receptors
Links: nuclear-receptor superfamily three classes | Image - Models of sex steroid action in target tissue

Eicosanoids

  • (icosanoids) prostaglandins, prostacyclins, thromboxanes and leukotrienes
  • lipids acting as signaling molecules
    • made from essential fatty acids (EFAs) oxidation (arachidonic acid)
  • act by binding to cell surface receptors, rapidly broken down (anti-inflammatory drugs act by downregulating eicosanoid synthesis)
  • act locally in autocrine or paracrine signaling pathways


Links: Eicosanoid biosynthesis cartoon | Prostaglandins

Nitric Oxide

  • (nitrogen monoxide) another signaling method that crosses lipid membranes
  • simple gas, very quick short-lived signal
    • synthesised from arginine by nitric oxide synthase
  • does not bind intracellular receptor
    • regulates intracellular enzymes

Example - dilation of blood vessels. (nitroglycerine for heart converted to NO)

References

Textbooks

Essential Cell Biology

  • Essential Cell Biology Chapter 15

Molecular Biology of the Cell

Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter New York and London: Garland Science; c2002

Molecular Cell Biology

Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James E. New York: W. H. Freeman & Co.; c1999

The Cell- A Molecular Approach

Cooper, Geoffrey M. Sunderland (MA): Sinauer Associates, Inc.; c2000

Search Online Textbooks

Books

PubMed

  • PubMed is a service of the U.S. National Library of Medicine that includes over 18 million citations from MEDLINE and other life science journals for biomedical articles back to 1948. PubMed includes links to full text articles and other related resources. PubMed
  • PubMed Central (PMC) is a free digital archive of biomedical and life sciences journal literature at the U.S. National Institutes of Health (NIH) in the National Library of Medicine (NLM) allowing all users free access to the material in PubMed Central. PMC
  • Online Mendelian Inheritance in Man (OMIM) is a comprehensive compendium of human genes and genetic phenotypes. The full-text, referenced overviews in OMIM contain information on all known mendelian disorders and over 12,000 genes. OMIM
  • Entrez is the integrated, text-based search and retrieval system used at NCBI for the major databases, including PubMed, Nucleotide and Protein Sequences, Protein Structures, Complete Genomes, Taxonomy, and others Entrez

Search Pubmed

Reviews

<pubmed>23838532</pubmed> <pubmed>21346732</pubmed> <pubmed>18396093</pubmed>| PMC <pubmed>18163464</pubmed>] <pubmed>17189856</pubmed> <pubmed>17630848</pubmed>

Articles

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name.


2017 Course Content

Moodle

Lectures: Cell Biology Introduction | Cells Eukaryotes and Prokaryotes | Cell Membranes and Compartments | Cell Nucleus | Cell Export - Exocytosis | Cell Import - Endocytosis | Cytoskeleton Introduction | Cytoskeleton - Microfilaments | Cytoskeleton - Microtubules | Cytoskeleton - Intermediate Filaments | Cell Mitochondria | Cell Junctions | Extracellular Matrix 1 | Extracellular Matrix 2 | Cell Cycle | Cell Division | Cell Death 1 | Cell Death 2 | Signal 1 | Signal 2 | Stem Cells 1 | Stem Cells 2 | Development | 2017 Revision

2017 Laboratories: Introduction to Lab | Fixation and Staining |


2017 Projects: Group 1 - Delta | Group 2 - Duct | Group 3 - Beta | Group 4 - Alpha

Dr Mark Hill 2015, UNSW Cell Biology - UNSW CRICOS Provider Code No. 00098G