![Page 1: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/1.jpg)
Cell Signaling
2007
![Page 2: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/2.jpg)
• Cells sense and send information (signals)• Cells communicate with each other• Cells must sense and respond to changes in
the environment
The signal can come from inside the cell, from another cell, or from the environment.
©2004 Lee Bardwell
Cell Signaling
![Page 3: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/3.jpg)
Generic Signaling Pathway
Signal
Receptor (sensor)
Transduction Cascade
OutputSomething
happens
outside
inside (cytosol)
©2002 Lee Bardwell
![Page 4: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/4.jpg)
Something
happens
Responses to cell signaling
• Gene expression is altered at the level of transcription, RNA processing or translation
• Enzyme activities are altered• Protein-protein interactions are induced or
inhibited• The localization of certain proteins and other
stuff is altered
biochemically
©2002 Lee Bardwell
![Page 5: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/5.jpg)
Something
happens
Responses to cell signaling
The Cell…– divides or stops dividing– differentiates– commits suicide or kills something– moves somewhere or stops moving– alters its metabolism– passes on the signal
Physiologically
©2002 Lee Bardwell
![Page 6: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/6.jpg)
What can be a signal?- almost anything
• Peptides - insulin, glucagon...• Proteins• Amino acid derivatives - epinephrine, histamine• Other small biomolecules - ATP• Steroids, prostaglandins• Gases - Nitric Oxide (NO)• Photons• Damaged DNA• Odorants, tastants
©2002 Lee Bardwell
![Page 7: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/7.jpg)
Steroid Hormone Signaling Pathway
Signal
(steroid)
Receptor (txn factor)
![Page 8: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/8.jpg)
Steroid Hormone Signaling Pathway
Output
∆ gene expression
∆ cell physiology
![Page 9: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/9.jpg)
Signaling cascades have many steps
Past:Enumeratecomponents
Now:• Modules• Circuits/ Design Logic• Cross-talk• Specificity
![Page 10: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/10.jpg)
Adrenaline signaling
• Signal: Adrenaline (epinephrine)– Secreted by adrenal gland
• Receptor: -adrenergic receptor
• Response:– Breakdown of glycogen to glucose to
provide energy for “fight-or-flight”
![Page 11: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/11.jpg)
Insulin signaling
• Signal: insulin– Secreted by cells of pancreas
• Receptor: a receptor kinase• Response:
– Sugar is taken up from bloodstream into cells
• Diabetes - type 1, type 2
![Page 12: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/12.jpg)
Growth factor signaling
![Page 13: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/13.jpg)
The growth of multicellular organisms is regulated by more than just nutrient availability
NUTRIENTS
NUTRIENTSunicellulareukaryote
multicellulareukaryote
a edigner
![Page 14: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/14.jpg)
Cells in multicellular eukaryotes require permission signals from growth factors
NUTRIENTS
NUTRIENTS
a edigner
![Page 15: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/15.jpg)
Disregulation of growth factor signal transduction leads to cancer
NUTRIENTS
cellulartransformation
NUTRIENTS
![Page 16: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/16.jpg)
Some growth factors
• EGF - epidermal growth factor
• FGF - fibroblast growth factor
• NGF - nerve growth factor
• PDGF - platelet-derived growth factor
• Insulin-like GF
All of these bind to a class of receptors known as “Receptor Kinases”
![Page 17: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/17.jpg)
Receptors with enzymatic activity
![Page 18: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/18.jpg)
Protein kinases and phosphatases
- Add/remove phosphates to/from proteins
- Involved in all signaling from cell surface recetors, and in most other signaling too
©2002 Lee Bardwell
![Page 19: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/19.jpg)
Protein Kinase Reaction
Kinase
Substrate
P P PPATP
![Page 20: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/20.jpg)
P P P
Protein Kinase ReactionPhosphorylation of protein substrates
Product
![Page 21: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/21.jpg)
Phosphorylation can flip a protein from “active” to “inactive” or vis-versa
ATP
ADP
![Page 22: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/22.jpg)
RAF
MEK
MAPKMAPK
TXY TXY
MEKPP
PP
P P
SP TP SP TP
The Mitogen-Activated Protein Kinase (MAPK) Cascade
![Page 23: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/23.jpg)
Neoplastic phenotype
Ras
MEKK
MEK/MAPKK
MAPKs
Raf
receptor
growth factor
MEK1
ERK1 ERK2
MEK2
Elk1/SRF
HER2
Fos Jun
FOS
CCND1
cyclin D1
![Page 24: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/24.jpg)
How do protein kinases
recognize their protein
substrates ?
Specificity in MAPK Signalling
![Page 25: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/25.jpg)
Protein Kinase Reaction
Kinase
Substrate
P P PPATP
![Page 26: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/26.jpg)
P P P
Protein Kinase ReactionPhosphorylation of protein substrates
Product
![Page 27: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/27.jpg)
Active site - target peptide interaction is not enough for
specificity
Kinase
Substrate
![Page 28: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/28.jpg)
Tethering function:Tethering function: Grewal et al (2006) Cell. Grewal et al (2006) Cell. Signal. 18:123Signal. 18:123
![Page 29: Cell Signaling 2007 Cells sense and send information (signals) Cells communicate with each other Cells must sense and respond to changes in the environment](https://reader035.vdocuments.us/reader035/viewer/2022062221/56649dc65503460f94abaad4/html5/thumbnails/29.jpg)
Bardwell Lab
• Lee Bardwell• Jane Bardwell• Kandarp Shah• Lamar
Blackwell• Tom Whisenant• Jeff Rogers• Pascal Krotee