Cell Singaling

8/11/2019 Cell Singaling

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Cell Signaling

2007


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Cells sense and send information (signals) Cells communicate with each other

Cells must sense and respond to changes inthe environment

The signal can come from inside the cell,from another cell, or from the environment.

2004 Lee Bardwell

Cell Signaling


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Generic Signaling Pathway

Signal

Receptor(sensor)

TransductionCascade

Output Something

happens

outside

inside (cytosol)

2002 Lee Bardwell


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Somethinghappens

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 otherstuff is altered

biochemically

2002 Lee Bardwell


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Somethinghappens

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


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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


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Steroid Hormone Signaling Pathway

Signal(steroid)

Receptor(txn factor)


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Steroid Hormone Signaling Pathway

Output gene expression

cell physiology


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Signaling cascades have many steps

Past:Enumeratecomponents

Now: Modules Circuits/

Design Logic Cross-talk Specificity


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Adrenalinesignaling

Signal: Adrenaline (epinephrine) Secreted by adrenal gland

Receptor: b -adrenergic receptor

Response: Breakdown of glycogen to glucose to

provide energy for fight -or- flight


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Insulinsignaling

Signal: insulin Secreted by b cells of pancreas

Receptor: a receptor kinase Response:

Sugar is taken up from bloodstream intocells

Diabetes - type 1, type 2


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Growth factor signaling


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The growth of multicellular organisms isregulated by more than just nutrient availability

NUTRIENTS

NUTRIENTSunicellulareukaryote

multicellulareukaryote

a edi ner


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Cells in multicellular eukaryotes requirepermission signals from growth factors

NUTRIENTS

NUTRIENTS

a edigner


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Disregulation of growth factor signaltransduction leads to cancer

NUTRIENTS

cellulartransformation

NUTRIENTS


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Some growth factors

EGF - epidermal growth factor FGF - fibroblast growth factor NGF - nerve growth factor PDGF - platelet-derived growth factor

Insulin-like GFAll of these bind to a class of receptors known asReceptor Kinases


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Receptors with enzymatic

activity


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Protein kinases and

phosphatases - A dd /rem ov e pho sp ha tes to /f rom pro teins - Involved in all signaling from cell surface

recetors, and in most other signaling too

2002 Lee Bardwell


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Protein Kinase Reaction

Kinase

Substrate

P P P P

ATP


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P P P

Protein Kinase Reaction Phosphorylation of protein substrates

Product


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Phosphorylation can flip a protein fromactive to inactive or vis -versa

ATP

ADP


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RAF

MEK

MAPKMAPKTXY TXY

MEK PP

PP

P P

SP TP SP TP

The Mitogen-Activated Protein Kinase(MAPK) Cascade


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How do proteinkinases recognizetheir protein

substrates ?

Specificity in MAPK Signalling


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Protein Kinase Reaction

Kinase

Substrate

P P P P

ATP


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Active site - target peptide interactionis not enough for specificity

Kinase

Substrate


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Tethering function: Grewal et al (2006) Cell. Signal. 18:123


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Bardwell Lab

Lee Bardwell Jane Bardwell Kandarp Shah

Lamar Blackwell Tom Whisenant Jeff Rogers

Pascal Krotee

Documents

Cell Singaling