Cell Signaling Flashcards
Cell signaling
Is the process by which the cells communicate withe their environment and respond to the environmental cues
Stages of cell signaling
Reception
Signal transduction
Response
Chemical signals are classified to
Neurotransmitters
Hormones
Local chemical mediators
Types of signaling
1 auto crine(like the T lympho cytes by cytokines)
2 endocrine(by blood)
3 paracrine(neiboughing cells like in synapses)
4 juxta crine(by complimentary surface proteins that act as ligand and receptors like in gap junctions and antegen presenting cells (MHC) and T lymphocytes (receptor)
Ligand definition
Types
Ligand is any small molecule that binds specifically to a receptor
1 agonist when it binds to the receptor it activates it
2 antagonist when it binds to a receptor without activating it
3 partial agonist it stimulates a receptor but unable to produce maximal response
Receptor
Is a molecule that recognizas specifically a ligand or a family of ligands
In response to binding it regulates cellular processes
For a cell to respond to any chemical messenger must produce
A specefic receptor that can bind to and produce response
Properties of receptor binding sites
binding is specific.
The shape of binding site determines specificity
Binding is most often reversible
Binding a ligand to a receptor causes a conformational change and changes the activity of the molecule
no chemical modification occurs
Cellular delivery (low density lipoprotein, transferrin)
Cell surface receptors
- Extracellulardomain
- Transmembrane domain
- Intracellulardomain
Cell surface receptors
GPCR
Ligand gated ion channel (ion channel linked receptor)
Enzyme linked receptor
When a ligand binds to the receptor it opens a channel through the membrane and allow specific ions to pass through
Examples
Nicotenic receptor
GABA R
Glycine receptor
Receptors that belong to the family of ligand gated receptor all of then they have a similar ———subunit structure
And each sub unit has —- transmembrane domains one of them the ——- forms the lining of the pore
pentameric
4 M2
2- Enzyme-linked receptors
Their cytoplasmic part has un intrinsic enzymatic activity or its assocated with an enzyme
Binding a ligand to the receptor causes a conformational change that activates the intrinsic enzymatic activity it has two types
1 tyrosine kinase linked receptor(growth factor receptor like insulin receptor platelet derived growth factor epidermal growth factor )
2 guanylyl cyclase linked receptor(ANP receptor)
Tyrosine kinase linked receptor
It has kinase activity in the cytoplasmc domain that phosphorelate the tyrosin residues how it works
When a ligand mainly growth factor binds to the receptor it causes to similar receptors to dimer together and they auto phosphorelate their tyrosine residues which then they are recognized by effector enzymes that have phosphotyrosine recognition sites directly (SH2) or by transducing proteins (IRS-1)
Page 32 Glevec and Imatinib
GPCR spans the membrane ——times
And its bound to a protein called——-
7
G protein(GTP binding regulatory protein)
GP dissociates into
They transduce the message
GTP bound alpha subunit
Beta gamma subunit
Ion channels
Or enzymes like
Adenylate cyclase or phospholipase C
Examples for GPCR
Muscarinic receptors
Dopamine receptors
Adrenergic receptors
Smell and taste receptors
Serotonin (5-HT) receptors
Rodopsin receptors
In the resting state the intracellular receptors are stabilized by
heat shock or chaperone protein
Many molecules whose activities are modified by the binding of small chemicals, including drugs, are not strictly receptors
The term ——- is used to describe to those molecules that their basic function can be carried out with out binding to a ligand
Acceptor
Example
Inhibited by
dihydrofolate reductase ,sodium channels
Methotrexate,local anaesthetics
Heart rate decrease by which receptor located on SA node
M2