Ch. 16 Smartwork (Exam 3)

When cells respond to an extracellular signal, they most often convert the information carried by this molecule from one form to another. What is this process called?

signal transduction

Signal transduction begins when

the receptor on a target cell receives an incoming extracellular signal and then produces intracellular signaling molecules that alter cell behavior

When the hormone insulin is released into the bloodstream, what form of cell-cell signaling is being used?

endocrine

What does a target cell require to respond to an extracellular signal molecule?

• appropriate intracellular signaling pathways

• effector molecules that alter cell behavior in response to the signal molecule

• a receptor that recognizes the signal molecule

• access to the signal molecule

A target cell does not need to be able to produce and secrete a signal molecule to which it will respond. Instead,

it must be exposed to that molecule and posses the correct combination of receptors, intracellular signaling pathways, and effector proteins to engage in the appropriate response

In cell signaling, each receptor is generally activated by

only one type of signal molecule

Which molecule performs the primary signal transduction step in cell signaling?

receptor protein

The cell-surface receptor protein recognizes an extracellular signal and

generates new intracellular signals in response

Ion-channel-coupled receptors can

rapidly alter the membrane potential in response to signal binding

• this change in membrane potential changes the permeability of the membrane to a particular ion and a cell's excitability.

Once activated by GTP-binding, many proteins have

intrinsic GTP-hydrolyzing (GTPase) activity, and they shut themselves off by hydrolyzing their bound GTP to GDP

What is true of the GTP-binding proteins that act as moleculer switches inside cells?

they are active when GTP is bound

The action of protein kinases is opposed by

the corresponding protein phosphatses

Proteins that are activated by phosphorylation on a serine or threonine will be

inactivated by removal of that phosphate by a phosphatase

Intracellular signaling pathways can include both

tyrosine kinases and serine/threonine kinases

Many protein kinases themselves are activated by

phosphorylation

Serine/threonine kinases phosphorylate

intracellular proteins on serines or threonines

Tyrosine kinases phosphorylate

intracellular proteins on tyrosines

What type of receptors do steroid hormones generally employ?

nuclear receptors

What is true of the GTP-binding proteins that participate in intracellular signaling?

only trimeric GTP-binding proteins relay messages from G-protein-coupled receptors

When a G-protein is inactive,

GDP is bound to its alpha subunit

When an extracellular signal molecule binds to its receptor, the altered receptor activates

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

GTP hydrolysis and inactivation usually occur within

seconds after the G protein has been activated

• the inactive G protein is then ready to be reactivated by another activated receptor

Signaling via a GPCR ceases when what condition occurs?

the alpha subunit hydrolyzes its bound GTP

IP3 binds to and opens Ca2+ channels that are

embedded in the ER membrane

Diacylglycerol remains in the membrane where it helps

to recruit and activate protein kinase C (PKC)

When activates phospholipase C cleaves an inositol phospholipid, what happens to the small signaling molecules the enzyme produces?

IP3 is released into the cytosol, while diacylglycerol is retained in the membrane

Phospholipase C is a membrane-bound enzyme that

is activated by a G protein called G_q

• once activated it cleaves a membrane phospholipid to generate the small intracellular sinaling molecules IP3 and diacylglycerol

What are small incracellular signaling molecules?

• cyclic AMP

• diacylglycerol

• Ca2+

• IP3 (inositol 1,4,5-trisphosphate)

What are small intracellular signaling molecules often called?

second messengers

When activated by GPCR, what does adenylyl cyclase do?

converts ATP to cAMP

What is the correct order of signaling events that might be triggered by a GPCR that activates expression of a target gene via the production of cyclic AMP?

G protein → adenylyl cyclase → cyclic AMP → PKA → transcription regulator

How can cyclic AMP, generated by adenylyl cyclase at the plasma membrane, activate the transcription of target genes?

the cyclic AMP activates PKA, which can enter the nucleus and phosphorylate specific transcription regulators

When activated by the binding of Ca2+, calmodulin relays the Ca2+ signal onward by doing what action?

binding to Ca2+/calmodulin-dependent protein kinases

What steps are required in the activation of the G-protein signaling pathway?

• activated Galpha influences target proteins

• ligand binds to the G-protein-coupled receptor

• Galpha exchanged GDP for GTP

What alterations to the signaling pathway would lead to increased transcription by the CREB protein?

• inhibition of cAMP breakdown

• inhibition of GTP hydrolysis

What would increase phosphorylation of CREB by PKA?

blocking binding of the regulatory subunits to the catalytic subunits of PKA

Adding high levels of Ca2+ to the cytosol will

restore signaling and activation of PKC

Activation of PKC occurs through binding to

DAG and the continuing presence of Ca2+

What is required for PKC activation?

binding to DAG and continuing presence of Ca2+

Following the binding of an extracellular signal molecule, receptor tyrosine kinases (RTKs) do what?

form dimers in which each polypeptide chain cross-phosphorylates the cytoplasmic tail of its partner

What do the phosphorylated tyrosines on activated RTKs do?

they serve as binding sites for a variety of intracellular signaling proteins

Ras is activated by a Ras-activating protein that does what?

causes Ras to exchange GDP for GTP

Certain mutant Ras proteins cannot hydrolyze their bound GTP to GDP, and therefore cannot do what?

turn themselves off

An inability to hydrolyze its bound GTP renders

mutant Ras constitutively active

Pi 3-kinase acts by phosphorylating what molecules?

inositol phospholipids

Ras can exist in two different conformations/states, inactive and active. What describes the stably active state of Ras?

• Ras is bound to GTP

• switch 1 & switch 2 regions are in an active conformation

Specific amino acids, including Arg 789 in Ras-GAP and amino acids Gln 61 and Thr 35 in Ras, all playu an important role in Ras function. WHy are these amino acids important?

they help facilitate GTP hydrolysis by Ras

What is true of the Notch signaling pathway?

the tail of the cell-surface receptor travels to the nucleus where it regulates gene transcription

Activation of Notch triggers

its cleavage

• the receptors cytosolic tail enters the nucleus where it helps to activate the appropriate set of Notch-responsive genes