Chapter 16: Cell Communication71 cards

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Many of the intracellular signaling proteins behave as switches:

receipt of a signal causes them to toggle from an active state to an inactive state


proteins that act as molecular switches fall mostly into one of two classes:

1- largest class: activated/inactivated by phosphorylation 2- GTP-binding proteins: switch between active and inactive depending on whether GTP or GDP are bound to them


protein kinase

tacks a phosphate group onto the switch protein


protein phosphatase

takes a phosphate off


phosphorylation cascade

one protein kinase, activated by phosphorylation, phophorylates the next protein kinase in sequence, and so on, : amplification, distribution, and modulation


two main types of intracellular protein kinases:

- serine/threonine kinases - tyrosines


GTP-binding proteins

active/inact stated depends on whether GTP or GDP is bound


GTP-binding proteins GDP bound

inactive - caused by GTPase: hydrolyzing


cell-surface receptors fall into 3 main classes:

1- ion channel coupled receptors 2- GPCRs 3- enzyme coupled receptors


ion channel coupled receptors

allow a flow of ions across the membrane , which changes the membrane potential and produces electrical current



activate membrane bound , trimeric GTP-binding proteins (G proteins) which then activate either an enzyme or an ion channel in the plasma membrane, initiating a cascade


enzyme coupled receptors

act as enzymes or associate with enzymes inside the cell


the reason why a signal molecule can have two different effects in two types of muscle cells bc

there are different types of receptors in the different tissues thus generating different intracellular signals


ion-channel coupled receptors are responsible for

the rapid transmission of signals across synapses in the nervous system


when a NT binds to a ion channel coupled receptor, the receptor

alters its conformation so as to open or close an ion channel


GPCRs from the

largest family of cell surface receptors - more than 700 in humans


all GPCRs have a similar structure:

each is made of a single polypeptide chain that threads back and forth across the lipid bilayer seven times


when an extracellular signal molecule binds to a GPCR, the receptor protein

undergoes a conformational change that activates a G protein on the underside of the plasma membrane


G proteins are composed of

alpha beta and gamma subunits


in the unstimulated state, the alpha subunit has

GDP bound to it and the G protein is idle


when an extracellular ligand binds to a GPCR, the altered receptor

activates a G protein by causing the alpha subunit to decrease its affinity for GDP, which is then exchanged for GTP


the activation of the alpha subunit of the G protein is thought to

break up the G protein subunits, such that alpha+GTP move away from beta+gamma = both complexes activated


the amount of time that the alpha+GTP and beta+gamma complexes are activated is limited by

the behavior of the alpha subunit - intrinsic GTPase activity


cholera is an example of a disease caused by a problem with a shut-off mechanism for a G protein switch:

toxin modifies the alpha subunit of a G protein in the intestine, remaining in active state indefinitely causing excessive outflow of Cl- and water into the gut


whooping cough is an example of a disease caused by a problem with a shutoff mechanism for a G protein switch:

the alpha subunit is locked in its inactive GDP bound state = prolonged inappropriate signal - coughing


the reason why when Ach binds to receptors in heart muscle cells it inhibits the cell's electrical excitability is because

when the subunits break apart, beta+gamma binds to a K+ channel ALLOWING IT TO FLOW OUT


the two most frequent target enzymes for G proteins are

adenylyl cyclase--cAMP and phospholipase C--- inositol triphosphate and diacylglycerol


in the case of adenylyl cyclase, the activated G-protein subunit switches

on the adenylyl cyclase synthesizing cAMP from ATP


to terminate the signal when adenylyl cyclase is activated,

cAMP phosphodiesterase rapidly converts cAMP to AMP


caffeine inhibits

phosphodiesterase blocking cAMP degradation


cyclic AMP exerts most of its effects by

activating the enzyme cAMP dependent protein kinase


what does PKA do?

when activated, catalyzes the phosphorylation of particular series or threonines on certain intracellular proteins, altering them


once activated, phospholipase C propagates a signal by

cleaving a lipid molecule that is a component of the plasma membrane



an inositol phospholipid is a phospholipid with

the sugar inositol attached to its head


the signaling pathway that begins with the activation of phospholipase C is also called

inositol phospholipid pathway bc of the involvement of the inositol phospholipid


the phospholipase C pathway works in the following way: (3)

1- the phospholipase C chops off the sugar-phosphate head off the inositol phospholipid, generating IP3 and DAG 2- IP3 (water soluble) diffuses into the cytosol 3- DAG remains in the plasma membrane


when IP3 is cleaved in the phospholipase C pathway and released into the cytosol, what happens to it?

1-it encounters the ER where it binds and opens Ca++ channels 2-Ca++ rushes out signaling other proteins


what does the DAG cleaved from the inositol phospholipid in the phospholipase C pathway do?

recruits and activates a protein kinase C - C bc it needs Ca++ to be activated


Ca++ has a widespread role as a small intracellular messenger

egg to start development muscle contraction ***steep ECG at ER and PM



Ca++ binds to this Ca++ responsive protein, and it undergoes a conformational change, wrapping round target proteins


one of the positive advantaged of signaling cascades:

allows spectacular amplification and allows cells to adapt


adaptation allows cells to

remain sensitive to changes of signal intensity over a wide range o background levels of stimulation


enzyme coupled receptors are

transmembrane proteins that display their ligand binding domains on the outer surface of the plasma membrane but instead of associating with a G protein, the cytosolic domain of the receptor either acts as an enzyme or forms a complex with a protein that acts as an enzyme


enzyme coupled receptor response are typically

slow (hours) eventually lead to changes in gene expression


enzyme coupled receptors can mediate direct, rapid

reconfigurations of the cytoskeleton, controlling the way a cell changes its shape and moves


the extracellular signals for architectural alterations (cell change in shape and movement) are

often proteins attached to the surfaces over which a cell is crawling


enzyme coupled receptors have a major role in the development of diseases and disorders in

cell growth, proliferation, differentiation, survival, and migration


largest class of enzyme coupled receptors is made up of those with

a cytoplasmic domain that functions as tyrosine protein kinase called receptor tyrosine kinases


PKA, PKC, and CaM-kinases are all

serine/threonine kinases


the only tyrosine kinases we discussed were

RTKs - receptor tyrosine kinases


unlike the seven pass GPCRs, enzyme coupled receptors have

only one transmembrane segment = an alpha helix


enzyme coupled receptors have a different strategy for transducing an extracellular signal,

bc it only has one membrane spanning alpha helix. so - binding of the signal molecule causes: 1-two receptor molecules come together to form a dimer 2-activating kinase fxn 3- phosphorylate each other 4-triggers the assembly of elaborate intra. sign. complex


to help terminate the response in the RTK cascade,

tyrosine phosphorylations are reversed by protein tyrosine phophatases



small GTP-binding protein that is bound by a lipid tail to the cytoplasmic face of the PM


the Ras protein is a member of

a large family of small GTP-binding proteins (monomeric GTPases)


Ras resembles the

alpha subunit of a G protein and functions in much the same way: GTP bound GDP bound


MAP-kinase signaling module

three-kinase protein module that carries a signal from the PM to the nucleus



bind to receptors that can activate transcription regulators that are held in a latent state near PM BUT once activated head straight for the nucleus


in Drosphila, what intrinsic properties does a notch receptor possess ?

a transcription regulator: - activated by the binding of delta (attached to a neighboring cell) -notch receptor cleaved -releases cytosolic tail of the receptor - tail heads to nucleus -activates genes


the notch receptor- delta signal protein complex utilize

the simplest and most direct way known to transmit a signal from a cell-surface receptor to the nucleus