IM Lecture 6 Cell Signaling Pathways

Cell signaling occurs when…

A ligand binds to a receptor

Ligand

Small molecule that binds to a receptor and changes the cell actions

Receptor

Molecule that binds to ligands (can be on the surface or cytoplasm)

Ligands can vary in…

Complexity/structure, type of molecule (protein/carb/lipid), distance travel (endocrine, paracrine, autocrine)

What is the end result of cell signaling?

Transcriptional changes

Signal transduction pathway

The molecular route of a ligand-receptor interaction to cause a biochemical change

Affinity

Measure of the constant between 1 binding site and 1 ligand

Avidity

Sum of all the attractive forces between a receptor and ligand

Signal transduction general steps

Ligand binds to receptor, adaptor proteins transmit signal to cell, second messenger diffuses to other sites to stimulate metabolic change, protein kinases or phosphatase are activated, enzyme cascade to continue pathway

Results of signal transduction

Activation of immune cells, differentiation of cell types, initiation of specific functions, changes in synthesis of proteins

Receptor signalling in innate immunity include…

Alter transcription of binding PRRs to PAMPs to induce expression of cytokines

TLRs

Receptors of the innate immune system to recognize BROAD structures

TLR extracellular component

LRRs (leucine-rich repeats) when binded to a ligand induces dimerization

TLR intracellular component

TIR domain

TLR adaptor proteins

TRIF and MyD88

TRIF (TLR adaptor protein)

TIR domain induces IFN-B factor

MyD88 (TLR adaptor protein)

TIR domain induces NF-kB and MAPK pathways

TIRAP (sorting receptor)

Helps recruit MyD88 to TLRs

TRAM (sorting receptor)

helps recruit TRIF to both TLR3 and endosomal TLR4

TLR signaling

First part of pathway occurs in cytoplasm leading to activation of NFkB (transcription of cytokines)

TRIFs are primarily for…

Endosomal activation

MyD88 are primarily for…

Anti-microbials and cytokine production