receptors and their mode of signalling

communication Multicellular organisms require precise coordination of cellular activities

Communication par Substances solubles hormones neurotransmetteurs neuropeptides cytokines facteurs de croissance interleukines facteurs d’inflammation Cellules nerfs (par propagation d’un potentiel d’action) Image: Graham Johnson

Cells communicate with each other through first messengers

Communication, employing first messengers, occurs in different ways

one characteristic of cells is their protected interieur (only accessible through selective transport mechanisms)

The plasma membrane, surrounding the cell, is an efficient barrier for the majority of physiological substances

Transmembrane proteins are therefore essential to communicate with the cellular environment (other cells as well as extracellular matrix)

Langley proposed (around 1905) that first messengers, as well as exogenous substances that affect cellular functions, don’t interact with the entire cell but with small quantities of « receptive substances ».

membrane (and intracellular) receptors transmit signals from first messengers into the cell

The cellular response to a first messenger depends on the cellular context

Binding of insulin causes receptor trans-phosphorylation and signalling complex formation Here tyrosine phosphoresidues render the receptor active. The active receptor phosphorylates a docking protein (IRS1) which then attracts an effector protein PI 3-kinase

Modification of protein activity or function through post-translational modification  Addition of a phosphate (covalent), phosphorylation  Exchange of nucleotide (non-covalent interaction) -GDP for GTP (GTP-binding proteins and tubuline (microtubules) -ADP for ATP (motor proteins such as kinesine or myosine)  Addition of an ubiquitin (covalent)  Addition of a sugar group (covalent)  Addition of a fatty acid or isoprenoid

Modification of protein activity or function through post-translational modification  Addition of a phosphate (covalent), phosphorylation  Exchange of nucleotide (non-covalent interaction) -GDP for GTP (GTP-binding proteins and tubuline (microtubules) -ADP for ATP (motor proteins such as kinesine or myosine)  Addition of an ubiquitin (covalent)  Addition of a sugar group (covalent)  Addition of a fatty acid or isoprenoid

Modification of protein activity or function through post-translational modification  Addition of a phosphate (covalent), phosphorylation  Exchange of nucleotide (non-covalent interaction) -GDP for GTP (GTP-binding proteins and tubuline (microtubules) -ADP for ATP (motor proteins such as kinesine or myosine)  Addition of an ubiquitin (covalent)  Addition of a sugar group (covalent)  Addition of a fatty acid or isoprenoid