Signaling Machinery The Signals The Receivers Peptides & small organic molecules (hormones, amines) Signaling molecules are called ligands in general The Receivers Large proteins (protein complexes) Ligand binding alters conformations resulting in conveyance of signal

A Ligand Bound to Its Receptor Figures\Chapter15\High-Res\life7e-fig-15-03-0.jpg

Cell Signaling Cell A Cell B Changes in Cell Fate Differentiation Ligand activates receptor Ligand secreted Receptor Cell A Modulate activity of existing proteins Cell B Signaling cascades initiated Protein synthesis Gene Activation Changes in Cell Fate Differentiation Migration Proliferation

Categories of Signaling Molecules Growth factors (proliferation/differentiation) FGF, EGF, TGF, NGF, peptide hormones Retinoids/Steroids RA, Testosterone, Cortisone Differentiation Wnt, Hedgehog, Delta Cytokines Interferons, interleukins Migration Semaphorins, Ephrins Neurotransmitters Catecholamines, NO Other Odorants, capsaicin

Categories of Receptors Cytoplasmic/Nuclear Bind membrane soluble ligands – steroids/retinoids Directly affect transcription Transmembrane Receptor tyrosine kinases – growth factors Receptor serine kinases – growth factors Kinase-associated receptors - cytokines Seven-pass – neurotransmitters, peptide hormones Ligand-gated channels – neurotransmitters, ions Other – cell-associated ligands

Signaling Modes Autocrine Juxtacrine Paracrine Signal is received by secreting cell (as well as other cells) Juxtacrine Signal is transmitted only short distances to neighboring cells Signaling molecule is membrane anchored or associated with ECM Paracrine Signaling at a distance from source Growth factors, hormones, cytokines, etc. Figures\Chapter15\High-Res\life7e-fig-15-01-1.jpg

Two Locations for Receptors Figures\Chapter15\High-Res\life7e-fig-15-04-0.jpg

A Cytoplasmic Receptor Figures\Chapter15\High-Res\life7e-fig-15-08-0.jpg

A Gated Ion Channel Figures\Chapter15\High-Res\life7e-fig-15-05-0.jpg

A Protein Kinase Receptor Figures\Chapter15\High-Res\life7e-fig-15-06-0.jpg

A Protein Kinase Cascade Figures\Chapter15\High-Res\life7e-fig-15-09-0.jpg

G-Protein-Linked Receptor (7 Pass) Figures\Chapter15\High-Res\life7e-fig-15-07-1.jpg 2nd messenger

7-Pass Receptor Interacting with Trimeric G-Protein

Formation of Cyclic AMP 2nd Messenger Figures\Chapter15\High-Res\life7e-fig-15-10-0.jpg

Phospholipid Derived 2nd Messengers

IP3 and DAG 2nd Messengers phosphotidylinositol-4,5 - bisphosphate diacylglycerol Inositol-1,4,5-phosphate Figures\Chapter15\High-Res\life7e-fig-15-11-0.jpg

Calcium Ions as a 2nd Messengers Figures\Chapter15\High-Res\life7e-fig-15-12-0.jpg

Nitric Oxide as a 2nd Messenger Figures\Chapter15\High-Res\life7e-fig-15-13-0.jpg

Signal Transduction Pathway Opens Ion Channels Figures\Chapter15\High-Res\life7e-fig-15-14-1.jpg

Signal Transduction Pathway Opens Ion Channels Figures\Chapter15\High-Res\life7e-fig-15-14-2.jpg

Signaling Cascades Alter Enzyme Activity Figures\Chapter15\High-Res\life7e-fig-15-15-1.jpg

Gap Junctions Connect Some Animal Cells Figures\Chapter15\High-Res\life7e-fig-15-16-0.jpg

Plasmodesmata Connect Some Plant Cells Figures\Chapter15\High-Res\life7e-fig-15-17-0.jpg