Cell signaling

Prof.Dr.Gönül Kanıgür

Cell Signaling

• All cells receive and respond to signals from their surroundings

• Signaling molecules that are secreted on the surface of one cell and bind to receptors expressed by the other cells

• The binding of most signaling molecules to their receptors initiates a series of intracellular reactions that regulate of the cell behaviour including metabolism,movement,proliferation and differentiation

• The ligand is the signaling molecule.• It may be a hormone,a growth factor/cytokine

,a steroid,a polypeptide,or other type of molecule.It has no activity of its own,but must bind to a macromolecule

• Which is known as a receptor• Receptor when activated by ligand ,the

receptor causes a change in the target cell in which it is expressed

Signaling molecules

• Signaling molecules, which are released by signal-producing cells, reach and transfer biological signals to their target cells to initiate specific cellular responses.

signaling molecules

• Extracellular molecules

• Intracellular molecules

1. Extracellular molecules

protein & peptides: Hormone, cytokine

AA & its derivatives: Gly, Glu, adrenaline, thyroxine

Steroid: Sex Hormone, glucocorticosteroid

Fatty acid derivatives: prostaglandin

2. Intracellular molecule

• Ca2+ ions

• DG, ceramide lipid derivatives• IP3 carbohydrate

derivatives

• cAMP cGMP nucleotides

• Ras, JAK, Raf proteins

Effect by membrane receptors

Effect by intracellular receptors

Intracellular molecules

Extracellular molecules

Signal molecules

cAMP, cGMP, IP3, DG, Ca2+

Proteins and peptides:

Hormones, cytokines

Amino acid derivatives:

Catecholamines

Fatty acid derivatives:

Prostaglandins

Steroid hormones, Thyroxine, VD3

Cell Cell signalingMost signaling molecules are secreted by one cell

and bind to cell surface receptorsexpressed by a target cell.

The steroid hormones are small hydrophobic molecules that diffuse across the plasma membrane of their target cells and bind to intracellular receptors.

Signaling molecule

Receptor of target cell

Intracellular molecule

biological effect

Signaltransduction

Cell Cell signaling is divided into three general categories

• Endocrine• Paracrine • Autochrine • signaling based on the distance over which

signals are transmitted

(1) Endocrine signal

• Secreted by endocrine cells.• Reach target cells by blood circulation.• Time of action is long.• Such as insulin, thyroxine, adrenalin

(2) Paracrine signaling (local chemical mediators)

• Secreted by common cells.• Reach neighboring target cells by

passive diffusion.• Time of action is short.

(3) Synaptic signal (neurotransmitters)

• Secreted by neuronal cells.• Reach another neuron by synaptic gap.• Time of action is short.• Such as Acetylcholine (Ach), noradrenaline

(4) Gaseous signal

• Simple structure, half life is short and active in chemistry .

• Such as NO, CO.• NO is amajor paracrine signaling molecule

in the nervous,immune and circulary system

• .NO is synthesized from the aa arginine by the enzyme nitric oxide synthase.

(5) Autocrine signal

• Act back to their own cells.• Such as GF, cytokine, interferon, interleukin.

• Direct cell to cell signaling,some signaling molecules remain bound to the cell surface and act as a ligands.these kinds off signaling take place during embryonic development

Receptor

Receptors are specific membrane or intracellular proteins, which are able to recognize and bind to corresponding ligand molecules,

Receptor when activated by ligand ,the receptor causes a change in the target cell in which lt is expressed.

Glycoprotein or Lipoprotein

(1) Recognize the special ligand

(2) Binding to special ligand

(3) Signal transduction biological effect

Function of receptor

ligand　 A small molecule that binds specifically

to a larger one; for example, a hormone is the ligand for its specific protein receptor.

• Membrane receptors

membrane

Glycoprotein

• Intracellular receptors

Cytosol or nuclei

DNA binding protein

Properties of binding of Hormone and Receptor

• highly specificity

• highly affinity

• saturation

• reversible binding

• special function model