Biol 266 : Unit 7

Skipped PPT 21

Signal transduction: the process of ______________ an _______________ signal (signaling molecule A) into an ___________________ signal (signaling molecule B) in a ______________ cell.

converting ; extracellular ; intracellular ; target

Six steps in signaling ;

___________ of the signaling molecule by the signaling cell

___________ of the signaling molecule by the signaling cell

____________ of the signaling molecule to the target cell

____________ of the signal by a specific receptor protein

a ____________ in cellular metabolism, function,or development triggered by the receptor-signaling molecule complex

____________ of the signaling molecule, which terminates the cellular response

Synthesis ; release ; transport ; detection ; change ; removal

Signaling can be classified into 4 types that act over short or long distances:

Autocrine / Paracrine / Endocrine / Contact-dependent

In ____________________ signaling, cells respond to signaling molecules that they themselves release. This type of signaling is particularly common in cancer cells, which overproduce and release growth factors that stimulate inappropriate, unregulated growth and division of themselves, leading to cancer development

autocrine

In ____________ signaling, the signaling molecules released by a signaling cell into the extracellular medium act locally to affect target cells in close proximity to the signaling cel

paracrine

In ___________________ signaling, the signaling molecules, called hormones, act on target cells distant from their site of synthesis by endocrine cells. Hormones produced in endocrine cells are secreted into the bloodstream and can be distributed widely throughout the body.

endocrine

In ________________________ signaling, a membrane-anchored signal in the plasma membrane of the signaling cell binds to a receptor molecule embedded in the plasma membrane of the target cell. This requires cells to be in direct membrane-to-membrane contact with each other and does not require the release of a signaling molecule

contact-dependent

Each ______________ in a pathway alters the conformation or activity of the next protein. In some cases the intracellular signaling molecule can be a small molecule (e.g. cAMP, Ca2+). These are referred to as __________________.

protein ; second messengers

Protein conformation is usually altered by _______________. ___________add phosphate groups while ___________ remove them.

phosphorylation ; Kinases ; phosphatase

When signaling is mediated by proteins, upon activation of the signaling cascade there are four types of molecular switches:

phosphorylation-dephosphorylation / GTP binding / assembly-disassembly of protein complexes / proteolysis

Protein phosphorylation can change

protein behavior in different ways.

1. It can __________________ an

enzyme.

2. It can promote or interfere with

______________________.

3. It can _________ the subcellular location

of the protein.

4. It can trigger ________________.

activate or inactivate ; protein-protein interactions ; change ; protein degradation

Thus, a kinase tends to _______________ a signal and a phosphatase tends to _____________ a signal.

activate ; inactivate

In the ______________, the GTP-binding protein is bound to GDP.

absence of a signal

___________ activate the release of GDP and the subsequent binding to GTP.

Signals

Some proteins act as _______________ to bring other signaling molecules into proximity for sequential activation.

scaffolds

Most interactions during signaling are mediated by specific ___________________, stretches of amino acids that share some degree of similarity and can function independently of the entire protein.

protein domains

Protein interaction domain to remember :

SH2

SH3

PH

PTB

SH2 – binds to phosphate in a particular sequence SH3 – binds to proline-rich sequences PH – binds to certain phosphoinositides PTB – binds to phosphorylated tyrosine residues in a particular sequence

SH2 :

Binds to phosphate in a particular sequence.

SH3 :

Binds to proline-rich sequences.

PH :

Binds to certain phosphoinositides.

PTB :

Binds to phosphorylated tyrosine residues in a particular sequence.

Some signaling cascades are mediated by ___________ where the intracellular portion of the receptor is cleaved and acts as a signaling molecule.

proteolysis

In contrast to the other three molecular switches, proteolysis is ___________________: once the protein is cleaved it cannot be undone, whereas phosphorylation can be reversed by a phosphatase, GTP activation can be reversed by GTP hydrolysis, and protein assembly can be undone.

not reversible

The pathway can be thought of as a cascade of events. The cascade serves to:

1. ____________ the signal and help spread it in the cell.

2. __________ the signal such that a few extracellular molecules can provoke a large intracellular response.

3. ___________ the signal to a number of different effector proteins evoking a complex response.

4. ____________ signals from other pathways before relaying them onward

Relay ; Amplify ; Distribute ; Integrate

Amplification of the epinephrine signal: 1 molecule of ___________ leads to the production of 100x10^6 molecules of ____________________.

epinephrine ; glucose-1-phosphate

1st class (largest) of extracellular signalling molecule:

• extracellular signaling molecules are too ______ and too __________ to cross the plasma membrane

• receptors are on the ____________ of the plasma membrane of the target cell

large ; hydrophilic ; outer surface

2nd class of extracellular signalling molecule:

• extracellular signaling molecules are sufficiently _______ and _______ to diffuse across the plasma membrane

• receptors are in the ___________ of the target cell, either in the cytosol or in the nucleus

small ; hydrophobic ; interior

There are 3 classes of ligand-triggered cell-surface receptors:

1. _____________________ – found in virtually all cells .

2. _____________________ – especially important in neuronal signaling.

3. ____________________

G-protein-coupled receptors ; Ion-channel-coupled receptors ; Enzyme-coupled receptors

Some G proteins stimulate the production of cAMP and are referred to as __________. Others inhibit the production of cAMP and are called ________.

Gs ; Gi

Some G proteins stimulate the production of diacylglycerol and inositol-1,4,5-triphosphate by activating _________________ and are referred to as _________.

phospholipase C ; Gq

__________________ changes the conformation of the ion-channel-linked receptor and _________ the channel for ion flow

Ligand binding ; opens

An enzyme-coupled receptor binds its _______________ switching on an enzyme activity on the ______________ of the plasma membrane. The enzyme may be part of the cytoplasmic domain of the receptor (1) or it may be an enzyme that associates with the cytoplasmic domain of the receptor (2).

extracellular ligand ; opposite side

Two groups of small, diffusible signaling molecules:

1. __________________– their receptors are transcription factors that regulate expression of specific genes.

2. _________________ – Produced by the breakdown of arginine, short-lived so only local acting (paracrine signaling), important in the cardiovascular system.

Hormones ; Nitric oxide (NO)

_______________ is produced by the adrenal gland under stress and low blood glucose. It causes the body to produce ___________ and ____________ the immune system.

Cortisol ; glucose ; suppresses

Thyroxine receptor is located in the __________ and is bound to DNA either in the presence or absence of thyroxine. In the ____________ of thyroxine, the receptor binds to a repressor molecule to prevent gene transcription.

nucleus ; absence

NO is a ____________, causing the smooth muscle cells lining blood vessels to relax, allowing blood to flow more readily. Produced through the action of acetylcholine.

vasodilator

NO activates _______________, an enzyme that produces ________, a second messenger that activates a _________________ that phosphorylates specific substrates leading to smooth muscle cell relaxation and ________________.

guanylyl cyclase ; cGMP ; protein kinase ; vasodilation

What is the role of G proteins in a signaling pathway?

They hydrolyze GTP to initiate signaling

They act as a switch to turn activities on or off

They interact with ligands to initiate a signaling pathway

All of the above

They act as a switch to turn activities on or off

_________________ is an enzyme that cleaves certain phospholipids next to the phosphate group.

Phospholipase C