(1) Autocrine

(2) Paracrine

(3) Endocrine

(4) Neuronal

Type of signaling mechanism over a short distance

One cell in a mixed population secrets and binds its own ligand

Group of identical cells bind ligand

Can be contact dependent

Classification of signaling over a short distance

One cell in a population of phenotypically different cells secrets a ligand which is bound by these cells

Can be contact dependent

Characteristic of autocrine or paracrine signaling

Important in embryogenesis and recognition of cell types in tissues

Helps restrain cell growth (cancer)

Endocrine

Type of long distance cell signaling

Specialized endocrine cells secrete hormones into the blood stream to target

Example hormones: estrogen, progesterone, testosterone, insulin, glucagon, cortisol, epinephrine

Defect in endocrine signaling

Types I and II

Autoimmune disorder

Disrupted endocrine signaling

No insulin is produced in the pancreas

Paracrine signaling disorder

Insulin resistance: insulin binds to receptor but there is no response

Type of cell signaling over a long distance (axon) or short distance (synapse)

May deliver to only one cell

Two phases

(1) through neuron as electrical signal

(2) thriugh synapse to target via neurotransmitters

(1) Diffusion across PM (hydrophobic-NO and steroid)

(2) Binding and activation of cell surface receptors (epi, glucagon, insulin)

Diffuse across PM and bind to intracellular receptor in cytosol

Bind DNA sequence and cause transcript and translation

Ex. testosterone, estradiol, progesterone, cortisol, aldosterone

Gas produced by endothelial cells to relax smooth muscle cells

Can diffuse across PM of smooth muscle to cause vasodilation

Requires nerve terminal (Ach signals endothelial to make NO), endothelial cells (synthesize NO using NOS), and muscle cells (target)

NO binds guanylyl cyclase in muscle which produces cGMP-->relaxation of cell

Found in endothelial cells

Convert arginine to NO and citrulline

Target protein for NO

Binds to Fe in active site producing cGMP which results in smooth muscle relaxation

Prodrug that produces NO without NOS

Used to treat angina-chest pain associated with lack of oxygen in heart

Relaxes blood vessels around heart to stimulate blood flow

Quick response to extracellular signal

Phosphorylate serine, threonine, and tyrosine residues

Results in phosphorylation of a protein

Can turn protein on or off

Dephosphorylates a protein

Can turn protein on or off

Mediates hormone, neurotransmitter, and local signals

7 alpha helices 

Heterotrimeric (alpha, beta, gamma)

GTPase activity

GalphaI and GalphaS-->adenylate cyclase

GalphaQ-->PLC

Molecular clock--will hydrolyze GTP after period of time to deactive itself

Activated by alpha subunit of GPCR

Stimulated by glucagon and epi

Converts ATP to cAMP

Formed by adenylate cyclase

Binds to PKA 

Activated by cAMP

Tetramer: 2 regulatory, 2 catalytic

4 cAMP bind to 2 regulatory (2 each) releasing regulatory from catalytic

Catalytic begin phosphorylation cascade

Serine/ threonine kinase

Activate adenylate cyclase

Beta adrenergic

GalphaS subunit

Activates adenylate cyclase

Epi stimulated

Inhibit adenylate cyclase

Alpha2 adrenergic

Stimulated by Epi and glucagon

GalphaI subunit

Inhibits adenylate cyclase

Converts cAMP to AMP

Stops signal

Phospholipase C

PLC

Use Gqsubunit as activator

Cleaves PIP2 forming IP3 and DAG

Formed from PIP2

Enter cytosol to bind to ER proteins and release Ca2+

Ca2+ binds to PKC

Protein Kinase C

PKC

Activated by Ca2+ released via IP3 activity

PKC is recruited to the membrane where it binds to DAG (formed from PIP2) and is activated

Can now begin phosphorylation cascade

Activated by Ca2+ released by IP3

Binds 2 Ca2+

Binds CamII Kinase

Activated by calmodulin

Causes autophosphorylation which makes it unnecessary to have calmodulin bound to it for activity

Receptor Tyrosine Kinase 

RTK

Activated by insulin or growth factors

When ligand bind monomers dimerize and tyrosine transautophosphorylate

Bind GRB2

Part of RTK pathway

Binds SOS

Part of RTK pathway

GEF-guanine exchange factor

Recruits Ras and influences Ras to exchange its GDP for a GTP

Guanine Exchange Factor

GEF

Stimulates protein to bind GTP

Gets Energized Form

GTPase Activating Protein

GAP

Stimulates GTPase activity-->convert GTP to GDP

Give A Phosphate

Monomeric alpha subunit with GTPase activity

Lipid embeds in membrane

Activates Raf Kinase

First kinase of RTK pathway

Stimulates cell division