Basics of Signal Transduction Ebaa M Alzayadneh, PhD

What is signal transduction?

Cell signaling The science of understanding how individual cells sense their environments and respond to stimuli... how so many functionally different cells can come from one fertilized egg?

Signaling is responsible for how cells can respond to their environment and how they can differentiate or change over time

Objectives Know the basics concepts of signal transduction Know specific mechanisms Membrane Receptor mediated (very diverse group) G-protein coupled Ion channel-linked Enzyme linked (example will be Receptor Tyrosine Kinases) Receptors that link to proteases Non-membrane receptor mediated pathways NO pathway Steroid hormone receptors

Communication by Extracellular Signaling usually involves: 1. Synthesis of the signaling molecule by the signaling cell 2. Release of the signaling molecule by the signaling cell 3. Transport of the signal to the target cell 4. Binding of the signal by a specific receptor protein 􀃆 conformational change 5. Initiation of intracellular signal-transduction pathways by the activated receptor 6. A change in cellular metabolism, function, structure, or development triggered immediately by the receptor-signal complex 7. Usually deactivation of the receptor 8. Removal of the signal, which usually terminates the cellular response -Additionally: Receptors also exist that bind and react to metabolites (oxygen, sugar, NO....)or physical stimuli (touch, light, heat....) In which case step 4-8 still apply

Basic concepts The same signal can induce different responses in different target cells Different combinations of signals induce different responses Responses can be fast or slow Signals are mediated by two types of receptors Signals are relayed and amplified

Signals get translated into cellular responses or changes in gene expression

Not all of the receptor needs to be bound to induce a response

Signals can act locally or at a distance

Basic types of signaling

The same signal can produce a different response in different targets

Different combinations of signals induce different responses

Responses can be fast or slow

Signals are mediated by two types of receptors

Signals are amplified

Major components of signaling pathways Signals Receptors G-proteins Protein kinases Protein phosphatases Second messenger producing components

Signaling is very conserved The same machinery is used in many different signaling pathways Different cell types will use the same machinery for different purposes

Proteins involved in signaling are conserved Human, C. elegans, drosophila; 1500 genes in common; 28% of this common set are involved in Signal transduction, 33% are of unknown function Proteins involved in signaling are conserved

Extracellular and intracellular What are signals? Extracellular and intracellular

Extracellular signals Physical Light, heat, touch, magnetic, electric Chemical Growth factors, hormones, nutrients, environmental cues Typically these initiate an action

Receptors determine response No receptor - no response

Intracellular signals We will focus on intracellular signals Secondary messengers Other types of signals (will see later) Typically these propagate or amplify an extracellular signal Some mediate internal signals Examples of hormones signaling pathways

Small organic molecules as signals Calcium can also be a signal

Other types of signals Changes in phosphorylation states Changes in ionic (Vm) composition Changes in what a protein is bound to Changes in protein structure

Extracellular signal receptors And the machinery that transmits their signals

Membrane bound receptors come in different forms