Advanced Molecular Genetics-Biology 566 Signal Transduction - First Messengers and Receptors
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First messengers

Hormones

-Endocrine messengers act at a distance on cells

-Paracrine messengers act on local cells

-Autocrine messengers act on the same cell

Growth Factors - Plasma derived growth factor (PDGF), EGF, Insulin, Transferrin

Cytokines - immune system communication messengers

Vasoactive agents - respond to tissue damage, prostaglandins.

Neurotransmitters and neuropeptides - glutamate, acetylcholine.

Lipophilic hormones - steriod hormones pass through membrane and bind cytoplasmic receptors.

Receptors

Animation of signal transduction

PDF file with text on receptors

7-Transmembrane helix receptors (7TMHRs) - base for a number of receptors.

May contain moieties that are reactive to external stimuli, such as rhodopsin is to light.

7TMHRs can form the basis for binding of a number of effectors.

Additional groups are added to accomodate the specificity and state changes in the 7TMHRs.

An additional parallel beta sheet/helix headpiece is added to accomocate the binding of large proteins to the receptor.

This arrangement of extracellular domains is typical for binding of cytokines, growth factors, differentiation factors and apoptosis inducing factors.

Many of these receptors carry cytoplasmic effector domains with tyrosine kinase activity.

Single receptor sites must dimerize in order to activate cytoplasmic domains.

Some channels are made up of beta sheets. These channels can be regulated as their change their conformation, for example, in a voltage dependent manner.

Does the concentration of receptors have an impact on activation? What about overproduction of receptors?

What impact would formation of heterodimers potentially have?

How does one experimentally work with membrane receptors?