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• Binding of the messenger to specific Binding of the messenger to specific target cell proteins known as target cell proteins known as receptorsreceptors

• Cell response to that messengerCell response to that messenger

Cell CommunicationCell Communication

• Receptors are proteins located either Receptors are proteins located either in the cell membrane or inside the in the cell membrane or inside the cell (nucleus)cell (nucleus)

• The messenger bind to the The messenger bind to the extracellular portionsextracellular portions

• Receptors are specificReceptors are specific

Cell CommunicationCell Communication

• Cytosolic Cytosolic oror Nuclear Nuclear– Lipophilic ligand Lipophilic ligand

enters cellenters cell– Often activates Often activates

gene gene

• Cell membraneCell membrane– Lipophobic ligand Lipophobic ligand

can't enter cellcan't enter cell– Outer surface Outer surface

receptorreceptor

Receptor locationsReceptor locationsReceptor locationsReceptor locations

ModulationModulation of Signal Pathways of Signal Pathways by Ligandsby LigandsModulationModulation of Signal Pathways of Signal Pathways by Ligandsby Ligands

Regulation of ReceptorsRegulation of Receptors

• Down regulation: when a high Down regulation: when a high extracellular concentration of a extracellular concentration of a messenger is maintained for some messenger is maintained for some time, the total number of the target time, the total number of the target cells receptors may decreased cells receptors may decreased

• Up regulation: cells exposed to low Up regulation: cells exposed to low concentration of a messenger, concentration of a messenger, develop sensitivity to it develop sensitivity to it

Signal Transduction Signal Transduction PathwaysPathwaysSignal Transduction Signal Transduction PathwaysPathways

Basic Mechanisms of Chemical SignalingBasic Mechanisms of Chemical Signaling

Pathways initiated by Pathways initiated by intracellular receptorintracellular receptor

Membrane Receptor ClassesMembrane Receptor ClassesMembrane Receptor ClassesMembrane Receptor Classes

• Plasma membrane receptor (lipid Plasma membrane receptor (lipid insoluble)insoluble)

1.1. Receptors function as ion channelReceptors function as ion channel

2.2. Receptor function as enzymeReceptor function as enzyme

3.3. Receptors that bound to and Receptors that bound to and activate cytoplasmic JAKactivate cytoplasmic JAK

4.4. Receptors activate G proteinReceptors activate G protein

General termsGeneral terms

• First messengers: Messengers bind to First messengers: Messengers bind to specific receptor.specific receptor.

• Second messengers: non-protein Second messengers: non-protein substances enter the cytoplasm and substances enter the cytoplasm and diffuse throughout the cell and transmit diffuse throughout the cell and transmit signalssignals

• Protein kinase: any enzymes that Protein kinase: any enzymes that phosphorylates other proteins by phosphorylates other proteins by transferring phosphate grouptransferring phosphate group

Protein receptor constitute of ion channelActivation of the receptor by the first messenger

The opening results increase diffusion of ions to the channel

Receptor function as ion Receptor function as ion channelschannelsReceptor function as ion Receptor function as ion channelschannels

•Receptors that posses intrinsic enzyme activity are all protein kinases•Binding of specific messenger to the receptor changes conformation•Enzymatic portion in cytoplasm is activated•The receptor phosphorylates its own tyrosine groupThe phosphotyrosine bind other protein which leads signaling pathways within the cell

Receptor functions as Receptor functions as enzymeenzymeReceptor functions as Receptor functions as enzymeenzyme

• The enzymatic activity reside not in the The enzymatic activity reside not in the receptor but in the separate cytoplasmic receptor but in the separate cytoplasmic kinaseskinases

The binding of the first messenger to the The binding of the first messenger to the receptor causes conformational changes receptor causes conformational changes that leads to activation of the JAK kinasethat leads to activation of the JAK kinase

The results of these pathways is the The results of these pathways is the synthesis of new proteins which mediate synthesis of new proteins which mediate the cells response to the messenger the cells response to the messenger

Receptor interact with Receptor interact with cytoplasmic JAK Kinases cytoplasmic JAK Kinases Receptor interact with Receptor interact with cytoplasmic JAK Kinases cytoplasmic JAK Kinases

Receptors that interact with G Receptors that interact with G proteinprotein

• G Protein is a protein bound to the G Protein is a protein bound to the receptor located on the inner receptor located on the inner cytosolic surface of the plasma cytosolic surface of the plasma membranemembrane

•Activation of the receptor by binding of the first messenger•G protein activated•G protein stimulate effector protein adenylate cyclase•Conversion to cAMP•cAMP act as second messenger•Cell response to the first messenger

Receptors that interact with G Receptors that interact with G proteinsproteinsReceptors that interact with G Receptors that interact with G proteinsproteins