Cell bio - ch 16 review

Discipline: Biology (and other Life Sciences)

Type of Paper: Question-Answer

Academic Level: Undergrad. (yrs 3-4)

Paper Format: APA

Pages: 1 Words: 275

Question

proteins, peptides, amino acids, nucleotides, steroids, fatty acid derivatives, or gas
Signal molecules can be _____, _____, _____, _____, _____, _____, or _____ --- but they rely on only a handful of basic styles of communication for getting the message across.

1) Endocrine: hormones produced in endocrine cells are secreted into the bloodstream & are distributed widely throughout the body.
2) Paracrine: signals (acting as local mediators) are released by cells into the extracellular fluid in their neighborhood & act locally.
3) Neuronal: neuronal signals transmitted along axons to remote target cells (via neurotransmitters)
4) Contact-dependent: a membrane-bound signal molecule on the signaling cell binds directly to a receptor protein on the target cell.
What are the 4 major ways that animal cells can signal to one another (communicate)? Briefly describe each.


-For a heart muscle cell: causes decreased rate & force of contraction
-For a salivary gland cell: causes secretion
-For a skeletal muscle cell: causes contraction
Different types of cells respond to the same signal in different ways. Give an example of this for the neurotransmitter acetylcholine.

cholesterol
What accounts for 20% of plasma membrane mass?

receptor proteins; working in combinations; fate
Every cell type displays a set of _________ that enables it to respond to a specific set of extracellular signal molecules produced by other cells. These signal molecules regulate the behavior of the cell by _________________. This is what controls cell _____ (i.e. whether the cell will survive, die, grow & divide, differentiate, etc).


increased cell growth & division; slowly (mins to hrs); more quickly (< sec to mins)
Certain types of cell responses -- such as _______________ -- involve changes in gene expression & the synthesis of new proteins; they therefore occur relatively _______. Other responses -- such as changes in ________, ________, or ________ -- need not involve changes in gene expression & therefore occur _______.

1) large/hydrophilic; cell-surface receptors
2) small/hydrophobic; intracellular enzymes; intracellular receptors
Extracellular signal molecules generally fall into 2 classes: 1) (largest class) consists of molecules that are _______ or _______ and cannot cross the plasma membrane of the target cell. They rely on ____________ to relay their message. 2) (smaller class) consists of molecules that are ________ or ________ and can easily slip across the plasma membrane. Once inside, they either activate _________ directly or bind ________ in the cytoplasm or nucleus.

steroid hormones; cholesterol
One important class of signal molecules that rely on intracellular receptor proteins is the ________ ________ --- including cortisol, estradiol, & testosterone --- which are made from ________.

These hydrophobic molecules pass through the the plasma membrane of the target cell & bind to receptor proteins located in the cytosol or nucleus (collectively called nuclear receptors). Upon hormone binding, the receptor undergoes a large conformational change that activates the protein, allowing it to promote or inhibit transcription of specific target genes. (note: receptors in the cytosol must move into the nucleus and bind to the regulatory sequence in DNA, while receptors in the nucleus are already bound to DNA).
Briefly describe how steroid hormones act as signal molecules in cells. (generalize)


B/c it is quickly converted to nitrates & nitrites (half life of ~ 5-10 seconds) by rxn with oxygen & water outside cells.
Why does NO only work locally?

guanylyl cyclase; Viagra
Inside many target cells, NO binds to & activates the enzyme _______ _______, stimulating the formation of cyclic GMP from GTP. Cyclic GMP forms the next link in the NO signaling chain that leads to the cell's ultimate response. The drug ________ blocks the enzyme that degrades cyclic GMP (cGMP-specific phosphodiesterase), prolonging the NO signal.

acetylcholine; endothelial; arginine; smooth muscle; proteins
Sequence of events leading to dilation of a blood vessel: ___ is released by nerve-terminals in the blood vessel wall & then diffuses to reach receptors on the surface of the ______ cells lining the blood vessel. There, it stimulates these cells to make NO from _____ & release it. NO diffuses into adjacent ______ cells where it regulates the activity of specific ______, causing muscle cells to relax.

1) relay
2) amplify
3) integrate
4) distribute
The components of intracellular signaling pathways (proteins or small messenger molecules; collectively called 'intracellular signaling molecules') perform one or more crucial functions. Name 4.

1) proteins that are activated (or inactivated) by phosphorylation; ex: P added covalently by a protein kinase that transfers the terminal P group from ATP to the signaling protein, turning it "on". protein phosphatase then removes the P, turning it "off".
2) GTP-binding proteins; ex: induced to exchange its bound GDP for GTP which turns it "on". Hydrolysis of the bound GTP to GDP then switches the protein "off".
Proteins that act as molecular switches fall mostly into one of two classes. What are they? Give an example of how each works.

1) ion-channel-coupled
receptors
2) G-protein-coupled receptors
3) enzyme-coupled receptors
Cell-surface receptors fall into 3 basic classes. What are they?

ion-channel-coupled; G-protein-coupled
Some signal molecules bind to receptors in more than one class. For example, the neurotransmitter acetylcholine acts on skeletal muscle cells via a _____________ receptor, whereas in heart muscle cells it acts through a ______________ receptor. (generate different intracellular signals & thus enable the 2 types of muscle cells to react to acetylcholine in different ways: contraction in skeletal muscle & relaxation in heart muscle).

7
G-protein-coupled receptors have ___ transmembrane domains.

3 (α, β, ϒ); 
α and ϒ;
α
All G proteins have a similar general structure. They are composed of ___ protein subunits (name them here) two of which are tethered to the plasma membrane by short lipid tails (name these 2 here). In the unstimulated state, the ___ subunit has GDP bound to it, & the G protein is idle.

Binding of an extracellular signal to the GPC receptor changes the conformation of the receptor which in turn alters the conformation of the bound G protein. The alteration of the α subunit allows it to exchange its GDP for GTP. This exchange triggers a conformational change (α subunit thought to detach from βϒ complex) that activates both the α subunit & the βϒ complex, which can now interact w/ their preferred target proteins/ion channels in the plasma membrane.
Briefly describe the general activation method of G proteins.

When an activated α subunit binds its target protein, it activates (or deactivates) the protein for as long as the 2 remain in contact. **Within seconds, the α subunit hydrolyzes its bound GTP to GDP. This loss of GTP inactivates the α subunit, which dissociates from its target protein & it reassociates with the βϒ complex to re-form an inactive G protein.
Briefly describe the general inactivation mechanism of G proteins.
enzymes or ion channels
The target proteins recognized by G-protein subunits are either ______ or ______ in the plasma membrane.

1) Binding of acetylcholine to its GPCR on heart muscle cells results in the activation of the G protein, Gi.
2) The activated βϒ complex binds to & directly opens a K+ channel in the plasma membrane, allowing K+ to flow out of the cell, decreasing the cell's electrical excitability.
3) Inactivation of the α subunit by GTP hydrolysis returns the G protein to its inactive state, allowing the K+ channel to close.
Briefly describe how the heartbeat in animals is slowed down (by GPCR in heart muscle cells). 3 major steps.

adenylyl cyclase, cyclic AMP (cAMP);
phospholipase C; inositol trisphosphate & diacylglycerol;
signaling proteins
The 2 most frequent target enzymes for G proteins are ________, the enzyme responsible for production of the secondary messenger (small intracellular signaling molecule) _____, and ________, the enzyme responsible for the production of 2 secondary messengers _____ & _____. The signal is greatly amplified at this step b/c many secondary messenger molecules are generated. They then diffuse to act on intracellular _________.

adenylyl cyclase; cyclic AMP phosphodiesterase

Cyclic AMP is synthesized by ________ & degraded by ________________.


cyclic AMP-dependent protein kinase (PKA); serines or threonines

Cyclic AMP exerts most of its effects by activating the enzyme _____________ (___). When activated, this enzyme then catalyzes the phosphorylation of particular _______ or _______ on certain intracellular proteins, thus altering the activity of the proteins.

The hormone adrenaline binds to & activates a GPCR that turns 'on' a G protein (Gs), which activates adenylyl cyclase. This boosts production of cAMP. cAMP then activates PKA which phosphorylates & activates phosphorylase kinase. This kinase phosphorylates & activates glycogen phosphorylase which causes glycogen breakdown. (note: does not involve changes in gene transcription/protein synthesis so occurs rapidly).

Give a specific example of cAMP effect in the cytosol of skeletal muscle. (Describe whole process)


Adrenaline binds & activates GPCR which turns 'on' a G protein (Gs), which activates adenylyl cyclase. This boosts production of cAMP. In the cytosol, cAMP then activates PKA which then moves into the nucleus & phosphorylates specific transcription regulators. These TR proteins then stimulate the transcription of a whole set of target genes. (note: occurs slowly); hormone synthesis in endocrine cells to production of proteins involved in long-term memory in the brain.

Give an example of cAMP effect in the nucleus. This type of signaling pathway controls many processes in cells ranging from _____________________ to _____________________.

A membrane inositol phospholipid is hydrolyzed by activated phospholipase C, which produces 2 secondary messenger molecules. 1) Inositol 1,4,5-trisphosphate (IP3) diffuses through the cytosol & triggers the release of Ca2+ from the ER by binding to & opening Ca2+ channels in the ER membrane. 2) Diacylglycerol remains in the plasma membrane &, together w/ Ca2+, helps activate the enzyme protein kinase C (PKC) recruited from cytosol to plasma membrane. PKC then phosphorylates its own set of intracellular proteins.

Briefly describe what takes place when the enzyme phospholipase C is activated by an activated G-protein alpha subunit.

1) Receptors with intrinsic enzyme activity (i.e. the cytoplasmic domain of the receptor acts as an enzyme itself); ex: receptor tyrosine kinases (RTKs)

2) Receptors without intrinsic enzyme activity (i.e. the cytoplasmic domain of the receptor forms a complex w/ another protein that acts as an enzyme); ex: prolactin receptor.

There are 2 classes of enzyme-coupled receptors. What are they? Give an example of each.


dimer; kinase; kinase; phosphorylates; tyrosines; interaction domain;

Typically, the binding of a signal molecule to the extracellular domain of an RTK causes 2 receptor molecules to associate into a _____. This brings the _____ domains of each receptor tail into contact w/ the other, activating their ____ function, w/ the result that each receptor ____ the other (on specific _____). This then stimulates the assembly of an intracellular signaling complex of proteins that bind b/c they possess a specialized ____ ____. These then help relay signal to cell's interior.

Ras

Virtually all RTKs activate ______: a small GTP-binding protein (a monomeric GTPase) that is bound by a lipid tail to the cytoplasmic face of the plasma membrane.


An adaptor protein docks on a particular phosphotyrosine on the activated RTK. The adaptor then recruits a Ras-activating protein that stimulates Ras to exchange its bound GDP for GTP, which activates it. (Ras can now stimulate several downstream signaling pathways).

Briefly describe how a RTK activates Ras.


three-kinase; MAP kinase; transcription regulators; protein activity & gene expression

(consequence of Ras activation): An activated Ras protein then activates a ___-___ signaling module, which relays the signal. The final kinase in the module, ______, phosphorylates various downstream signaling or effector proteins. These proteins can include other protein kinases &, most importantly, _____ _____. The resulting changes in ____ & ____ lead to complex change in cell behaviors such as proliferation & differentiation.

growth & survival

The PI-3-kinase-Akt signaling pathway is important in regulating cell ______ & ______.


PI 3-kinase; phosphorylates; lipid docking sites; Akt (*also called PKB!); serines & threonines
An extracellular survival signal activates an RTK, which recruits & activates _____ which then ______ inositol phospholipids in the plasma membrane. This then produces ____ ____ ____ in the plasma membrane that attract intracellular signaling proteins . One of these signaling proteins, ____, is a protein kinase activated by phosphorylation mediated by 2 other protein kinases. Once activated, its released from the plasma membrane & phosphorylates downstream proteins on specific ___.

A growth factor binds to RTK which activates the PI-3-kinase-Akt-signaling pathway . Akt then indirectly activates Tor (note: by phosphorylating & inhibiting a protein that helps keep Tor shut down). Tor (a serine/threonine kinase) stimulates protein synthesis while inhibiting protein degradation which casues cell growth (note: it does so by phosphorylating key proteins in these processes).Describe how Akt stimulates cells to grow.

The prolactin receptor is associated with a specific pair of JAKs (cytoplasmic tyrosine kinases). These JAKs first phosphorylate/activate each other, & then phosphorylate the receptor proteins. Transcription regulators called STATs bind to the receptor (where its phosphorylated) & the JAKs phosphorylate/activate the STATs. STATs disassociate, dimerize, & migrate to the nucleus where they help activate the transcription of milk protein genes.  
Briefly describe how prolactin receptors work, given the fact that they are enzyme-coupled receptors WITHOUT intrinsic enzy