General Signaling Principles
Outline notes: 1. Lecture - General signaling principles Geraint Thomas
Introduction
Failure in cell signaling influences the normal cell homeostasis and finally can results in diseases. (According to OMIM between 250-2500 diseases are related to genetic changes e.g. IBD, Huntington, etc)
Signals induce transitions from state 1 to state 2.
Even for staying alive cells need constant signaling.
Characteristics of a signal/change: - Perturbation from steady state - Reproducible - Managed - Controlled
Stimulus
Steroid hormones are lipophilic and can therefore diffuse across plasma membranes; they form signaling complexes with proteins
A signal binds a surface receptor ( induction of conformational change in the intracellular domain of the receptor ( transduction and amplification of the signal via downstream partners either linear or via network
Upon induction cells can start making signaling molecules that work either in an autocrine (same cell (type)) fashion or in a paracrine (other cells) fashion.
Adhesion molecules can also induce signaling; whether a cell is attached or not.
Signaling requires: - Coordination - Control in space - Control of time ( Spatial and temporal control): o When? o Where? o For how long?
Position – concentration – duration – sequence
Examples of stimuli: hormones, neurotransmitters, ions, lipids, Gfs, odorants, cytokines, photons, other cells etc…
Mediators have diverse properties: EM radiation, solubility, size, cleavage sites etc…
Cells can sense damage in nearby tissue for example by the release of ADP from injured cells
Examples for signaling molecules:
Neurotransmitters: Acetylcholine
Hormones: AA, peptides, fatty acids
Cytokines: TNF alpha (3x 185AA, 20kd) TGF beta 400 AA GM-CSF
Receptors
There is no pattern among signals, is there one among receptors?
Different
Introduction
Failure in cell signaling influences the normal cell homeostasis and finally can results in diseases. (According to OMIM between 250-2500 diseases are related to genetic changes e.g. IBD, Huntington, etc)
Signals induce transitions from state 1 to state 2.
Even for staying alive cells need constant signaling.
Characteristics of a signal/change: - Perturbation from steady state - Reproducible - Managed - Controlled
Stimulus
Steroid hormones are lipophilic and can therefore diffuse across plasma membranes; they form signaling complexes with proteins
A signal binds a surface receptor ( induction of conformational change in the intracellular domain of the receptor ( transduction and amplification of the signal via downstream partners either linear or via network
Upon induction cells can start making signaling molecules that work either in an autocrine (same cell (type)) fashion or in a paracrine (other cells) fashion.
Adhesion molecules can also induce signaling; whether a cell is attached or not.
Signaling requires: - Coordination - Control in space - Control of time ( Spatial and temporal control): o When? o Where? o For how long?
Position – concentration – duration – sequence
Examples of stimuli: hormones, neurotransmitters, ions, lipids, Gfs, odorants, cytokines, photons, other cells etc…
Mediators have diverse properties: EM radiation, solubility, size, cleavage sites etc…
Cells can sense damage in nearby tissue for example by the release of ADP from injured cells
Examples for signaling molecules:
Neurotransmitters: Acetylcholine
Hormones: AA, peptides, fatty acids
Cytokines: TNF alpha (3x 185AA, 20kd) TGF beta 400 AA GM-CSF
Receptors
There is no pattern among signals, is there one among receptors?
Different