Cellular Receptors Flashcards Preview

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Flashcards in Cellular Receptors Deck (27):

Why you have to study receptors?

-beta blockers in pharmacology
-Internal biochemical actions taking place
-TMX is used in the treatment of breast cancer


Cell communication

-chemical messenger (signal) secreted from a cell (source)
-travel to a target cell
-bind to a specific receptor (receiver)
-elicit a response


Messengers of nervous, endocrine, and immune system


Integration and co-ordination of various functions of the body require communications among organs, tissues and cells
-communication is mediated by chemical messengers



-macromolecule generally proteins that contain a binding site specific for a single chemical messenger
-another binding site involves in transmitting the message
-plasma membrane receptor or intracellular receptor



-chemical that bind with a high degree of specificity to a receptor
Ex: lnsulin, glucogon


Signal transduction

-chemical messenger binds to a receptor
-signal it is carrying must be converted into an intracellular response
-cascade reaction


Plasma membrane receptors

-span the plasma membrane
-helical in nature
-extra-cellular binding domain for the messenger
-not active until Logan binds and protein conformation changes


Ion-channel receptor (ligand gated)
-nicotinic acteylcholine receptor

-acetylcholine is the neurotransmitter at neuromuscular junctions
-subunits assemble around a channel that has a funnel-shaped opening in the center
-acetylcholine binds to the receptor, a conformational change opens the narrow portion of the channel (the gate), allowing Na+ to diffuse in and K+ to diffuse out
-change in ion concentration activates a sequence of events that eventually triggers the cellular response (contraction of the fiber)


Tyrosine Kinase Receptors

-generally exist in the membrane as monomers with a single membrane-spanning helix
-1 molecule of GF generally binds two molecules of the receptor and promotes their dimerization
-once dimer has formed, the intracellular tyrosine kinase domains of the receptor phosphorylate each other on certain tyrosine residues (autophosphorylation)
-phosphotyrosine residues form specific binding sites for signal transducer proteins


Serine-Threonine Kinase Receptors

- proteins in the transforming growth factor (TGF) superfamily use receptors that have serine-threonine kinase activity
-associate with proteins from the smad family, which are gene specific transcription factors
-superfamily include: TGF-beta-a cytokine/hormone involved in tissue repair, immune regulation and cell proliferation


Tyrosine Kinase associated receptors
--JAK-STAT Receptors

-used by cytokines, GH, and prolactin (PRL) to regulate the proliferation of certain cells
-receptor itself has no intrinsic kinase activity, but it binds the tyrosine kinase JAK (janus kinase)
-various cytosolic proteins such as STAT (Signal Transducers and Activators of Transcription) are phosphorylated by JAKs
-STAT-Ps dimerized enter the nucleus and activate transcription by binding to specific response elements


G-Protein coupled receptors (GPCR)

-only receptors with 2nd messengers
-translate a signal to a biologic effect inside cells
-GTP is the guanosine analogue of ATP
-G-proteins binds to GTP


One family of G-proteins (look on PPT for more detail)

-larger heterotrimeric G-proteins coupled to cell surface receptors and also effector proteins that catalyze the intra-cellular formation of second messengers
-G-proteins are made up of 3 sub-units designated as alpha,beta,gamma (trimeric protein associated with GTP)


Heptahelical or Serpentine Receptors

-heterotrimeric G protein-coupled receptors that have been characterized to date are proteins that span the cell membrane 7 times


Down regulation

-hormone or neurotransmitter is present in excess, the number of active receptors generally decreases


Up regulation

-in the presence of a deficiency of the chemical messenger, there s an increase in the number of active receptors



-ligand bind to their receptors, and the ligand-receptor complexes move laterally in the membrane to coated pits, where they are taken into the cell by endocytosis



-type of down regulation
-receptors are chemically modified in ways that make them less responsive



-bind with a high degree of specificity
-differ in their affinities for the receptors



-ligands that bind to receptors and cause a maximal response are often termed full agonists
-show much higher affinity for the receptor
Ex: Dexamethasone Agonist for Cortisol



-some ligand bind to receptors with high affinity yet elicit no response
Ex: Tamoxifen, antagonist for estrogen receptor to treat breast cancer


Partial agonist

-ligand that evoke a submaximal response, even when filling all the receptors
-affinity may not be great


Graves' Disease

-antibodies against thyroid stimulation hormone (TSH) receptors
-bugging eyes


Myasthenia gravis

-antibodies against nicotinic acetylcholine receptors
-muscle weakness and fatigue


3 modes of communication

1. Endo
2. Para
3. Auto


Two types of intracelular receptors

1. Cytoplasm
2. Receptors in the nucleus


Receptor diseases

-traced to mutations of the genes for receptors or for G-protein subunits