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Flashcards in Intracellular Signaling Deck (25)
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1

Cell Communication


•Each cell in a ____ ____ has been programmed to respond to specific ____ signals produced by other cells or the environment. These signals act in various combinations to regulate the _____ of the cell.
•Communication by extracellular signals usually involves a series of events:
1.____ of _____ ___ ____ in response to a ____
2.___ of the chemical messenger by the ____ cell
3.____ of the chemical messenger to the ___ cell
4.____ of the chemical messenger by a specific___ ____
5.___of an ___ ____ by the ___-___ ____(sometimes, the receptor is the ____)
6.____ in cellular ____ producing ____ ___ ___s, ___n, or ____ triggered by the effector
7____ through changes in protein ____ that could lead to changes in ___ and ___
8_____of the signal, which often____ the cellular response.



 


•Each cell in a multicellular animal has been programmed to respond to specific extracellular signals produced by other cells or the environment. These signals act in various combinations to regulate the behavior of the cell.
•Communication by extracellular signals usually involves a series of events:
1.Synthesis of extracellular chemical messenger in response to a stimulus
2.Release of the chemical messenger by the signaling cell
3.Transport of the chemical messenger to the target cell
4.Binding of the chemical messenger by a specific receptor protein
5.Activation of an effector protein by the messenger-receptor complex (sometimes, the receptor is the effector)
6.Change in cellular metabolism producing intracellular second messengers, function, or transcription triggered by the effector
7.Response through changes in protein function that could lead to changes in transcription and translation
8.Removal of the signal, which often terminates the cellular response.



 

2

Extracellular (____) Chemical Messengers/____/Signaling Molecules


•A few examples of chemical messengers are
____
___
____
___ ___


•General features of chemical messengers are
-They secreted by ____ cells in response to a ____
-The messenger ____ or is____ Through blood/other extracellular fluid to the ____ cell
-A receptor in the target cell ____ binds the messenger
-Binding of messenger to receptor elicits a _____
-The signal ___-and is terminated


•A few examples of chemical messengers are
-Neutrotransmitters
-Hormones
-Cytokines
-Growth factors


•General features of chemical messengers are
-They secreted by specific cells in response to a stimulus
-The messenger diffuses or is transported through blood/other extracellular fluid to the target cell
-A receptor in the target cell specifically binds the messenger
-Binding of messenger to receptor elicits a response
-The signal ceases and is terminated
 

3

Relationship between messenger producing cell and the target cell


A.Endocrine signaling – The chemical messenger (____) is secreted by a ____Cell type (_____ne ___), _____s the ____, which carries the signal to target cells distributed____ throughout the body.

B.Paracrine signaling – The chemical messenger secreted acts on ____ target cells. The secreted molecules are not allowed to __ ___ ___; for this reason they are often ___ ____up by ____target cells, ____ by extracellular enzymes. Ex-_____

C.Autocrine signaling – The chemical messenger acts on the cells from which it is ____. Ex – cellular _____ during ____t,

_____r cells often use autocrine signaling to overcome the normal controls on cell ___ and ____
 


A.Endocrine signaling – The chemical messenger (hormone) is secreted by a specific cell type (endocrine gland), enters the blood, which carries the signal to target cells distributed widely throughout the body.

B.Paracrine signaling – The chemical messenger secreted acts on nearby target cells. The secreted molecules are not allowed to diffuse too far; for this reason they are often rapidly taken up by neighboring target cells, destroyed by extracellular enzymes. Ex-neurotransmission.

C.Autocrine signaling – The chemical messenger acts on the cells from which it is secreted. Ex – cellular differentiation during development, cancer cells often use autocrine signaling to overcome the normal controls on cell proliferation and survival.
 

4

Note - Not all extracellular messengers are secreted

Contact-dependent signaling

Many signal molecules ___ ___ to the surface of the signaling cell and influence only cells that contact it. Such contact-dependent signaling is especially important ___ ____t and in ___ ____

Gap Junctions

Specialized cell-cell junctions that form between closely apposed plasma membranes and directly connect the____ of the joined cells via narrow _____- ____ channels. The channels allow the exchange of ___ _____ signaling molecules. Thus, cells connected by gap junctions can communicate with each other ___

Many signal molecules remain bound to the surface of the signaling cell and influence only cells that contact it. Such contact-dependent signaling is especially important during development and in immune responses.

Specialized cell-cell junctions that form between closely apposed plasma membranes and directly connect the cytoplasms of the joined cells via narrow water-filled channels. The channels allow the exchange of small intracellular signaling molecules. Thus, cells connected by gap junctions can communicate with each other directly.

5

Receptors


•Cellular response to a particular extracellular signaling molecule depends on its binding to a ____ receptor protein located on the surface of a t___ ____ (Cell surface receptors) or in its ___ or ____(Intracellular receptors).

•Binding of a signaling molecule (ligand) to its receptor is _____e, ie, the ligand “___,” a site on the receptor – similar to “lock and key mechanism” of enzyme-substrate reaction.

•Binding of a ligand to its receptor causes a _____ change in the receptor that initiates a ___ of ____leading to a specific cellular_____



•Signaling is specific because
-Typically ___ receptor binds only ___ specific messenger
-Only certain cells (target cells) carry ____ for the ____
-Each receptor initiates a characteristic ___ ___ ___.
 


•The extracellular messenger (ligand) is not metabolized to useful products, is not an intermediate in any cellular activity, and has no enzymatic properties. The only function of the ligand appears to be to change the properties of the receptor.


•Cellular response to a particular extracellular signaling molecule depends on its binding to a specific receptor protein located on the surface of a target cell (Cell surface receptors) or in its cytosol or nucleus (Intracellular receptors).

•Binding of a signaling molecule (ligand) to its receptor is selective, ie, the ligand “fits,” a site on the receptor – similar to “lock and key mechanism” of enzyme-substrate reaction.

•Binding of a ligand to its receptor causes a conformational change in the receptor that initiates a sequence of reactions leading to a specific cellular response.



•Signaling is specific because
-Typically one receptor binds only one specific messenger
-Only certain cells (target cells) carry receptors for the messenger
-Each receptor initiates a characteristic signal transduction pathway
 


•The extracellular messenger (ligand) is not metabolized to useful products, is not an intermediate in any cellular activity, and has no enzymatic properties. The only function of the ligand appears to be to change the properties of the receptor.
 

6

Cell surface receptors vs Intracellular receptors


•Cell surface receptors
1.Ligands are usually ___(hydrophilic) molecules that___ cross the plasma membrane
2.Have ___ ligand____ domains
3.Have one or more___ ____domains
4.Binding of ligand causes a____ change that is communicated to the ____ domain
5.Intracellular domain initiates a characteristic signal transduction pathway which can either cause a ____change in the cell or ____ changes through altering ___ and ____
 


•Intracellular receptors
1.Ligands are ____(hydrophobic) molecules which ___ cross the plasma membrane
2.Receptors are ___ ____
3.Binding of ligand causes a____change that allows its ___ to ___. 
4.Usually induce _____ changes through changes in transcription and translation 


•Cell surface receptors
1.Ligands are usually polar (hydrophilic) molecules that cannot cross the plasma membrane
2.Have extracellular ligand binding domains
3.Have one or more membrane spanning domains
4.Binding of ligand causes a conformational change that is communicated to the intracellular domain
5.Intracellular domain initiates a characteristic signal transduction pathway which can either cause a rapid change in the cell or slower changes through altering transcription and translation 
 


•Intracellular receptors
1.Ligands are non-polar (hydrophobic) molecules which can cross the plasma membrane
2.Receptors are transcription factors
3.Binding of ligand causes a conformational change that allows its binding to DNA
4.Usually induce slower changes through changes in transcription and translation 
 

7

Second Messengers


•Binding of ligands to many_________ receptors activates downstream effectors which stimulate a __-lived ____ (or decrease) in the concentration of the____ ___ ____s termed second messengers

•Either ___ or ___ from ____

•Act as ___ ____

•General characteristics of second messengers are

___ ____ in resting state

Regulated ___

Regulated____

Act through other ___


•Examples of second messengers are

  ___ ___ (____ and ___)

_____

 

  ___ ___ ( ____ and ____)

 

  


•Binding of ligands to many cell-surface receptors activates downstream effectors which stimulate a short-lived increase (or decrease) in the concentration of the intracellular signaling molecules termed second messengers

•Either synthesized or released from storage

•Act as intracellular ligands

•General characteristics of second messengers are

Low amounts in resting state

Regulated synthesis

Regulated destruction

Act through other proteins

 


•Examples of second messengers are

  Cyclic nucleotides

  cAMP

  cGMP

  Calcium

  Lipid derivatives

  Inositol triphosphate (IP3)

  Diacylglycerol (DAG)

  

8


G Protein-Coupled Receptors (GPCRs)


•Constitute the____ family of ___ ___ receptors

•Despite the ___ and ___ diversity of the signal molecules that bind to them, all GPCRs have a similar ____

•They consist of a ____ polypeptide chain that threads back and forth across the lipid bilayer ___ times and are therefore sometimes called “___ ____”, “_____” or “____” receptors

•Receptors that bind ___ ligands have a distinct, ____ extracellular domain 

•Receptors for small ligands such as ____ have ____ extracellular domains, and the ligand usually binds ___ within the plane of the membrane to a site that is formed by amino acids from ____ transmembrane segments

 


•Constitute the largest family of cell-surface receptors

•Despite the chemical and functional diversity of the signal molecules that bind to them, all GPCRs have a similar structure

•They consist of a single polypeptide chain that threads back and forth across the lipid bilayer seven times and are therefore sometimes called “seven transmembrane”, “heptahelical” or “serpentine” receptors

•Receptors that bind protein ligands have a distinct, large extracellular domain 
 


•Receptors for small ligands such as adrenaline have small extracellular domains, and the ligand usually binds deep within the plane of the membrane to a site that is formed by amino acids from several transmembrane segments

 

9


Activation of GPCRs and G proteins


•GPCRs activate _______ _____-binding proteins or _ proteins (composed of ____ protein subunits—___ ___ ___), which are anchored to the ____ leaflet of the plasma membrane

•In the unstimulated state, the receptor and G-proteins __ or __ ___ associate; the α subunit has ____ bound and the G proteins are __

•When extracellular signaling molecules bind to GPCRs, the receptor undergoes a ____ change, which in turn alters the confirmation of the ___ proteins

•α subunit releases its bound ___, allowing ___ to bind in its place, resulting in ____ change in α subunit. This causes the trimer to ____ from the receptor and into ___ ____components—an ___subunit and a __ complex-each then interacts with ___ downstream signaling proteins

 


•GPCRs activate heterotrimeric GTP-binding proteins or G proteins (composed of three protein subunits—α, β, and γ), which are anchored to the inner leaflet of the plasma membrane

•In the unstimulated state, the receptor and G-proteins may or may not associate; the α subunit has GDP bound and the G proteins are inactive


•When extracellular signaling molecules bind to GPCRs, the receptor undergoes a conformational change, which in turn alters the confirmation of the G proteins

•α subunit releases its bound GDP, allowing GTP to bind in its place, resulting in conformational change in α subunit. This causes the trimer to dissociate from the receptor and into two activated components—an α subunit and a βγ complex-each then interacts with different downstream signaling proteins

 

10


Inactivation of G proteins


•After α subunit activates its target protein (____ protein - either ___ or ___ ____), it shuts itself ___ by hydrolyzing its bound ___ to ____

•This ___ the α subunit, which dissociates from the t____ protein and ____s with a βγ complex to re-form an ____ G protein

•Binding to the _____ or to___ of ___ ___ ___ (RGS) usually stimulates the GTPase activity of the α subunit

•How does the GPCR itself get deactivated?
 


•After α subunit activates its target protein (effector protein - either enzymes or ion channels), it shuts itself off by hydrolyzing its bound GTP to GDP

•This inactivates the α subunit, which dissociates from the target protein and reassociates with a βγ complex to re-form an inactive G protein

•Binding to the target protein or to Regulators of G Protein Signaling (RGS) usually stimulates the GTPase activity of the α subunit

•How does the GPCR itself get deactivated?
 

11


Desensitization and inactivation of GPCRs


1.Ligand binds to ___
2.G-proteins ____ from GPCR
3.Desensitization of GPCRs begins with ____ of agonist -occupied receptors by ____ _____ (GRKs)
4.______binds to phosphorylated GPCRs, which sterically precludes coupling between the ___ and heterotrimeric ___
5.Receptor-bound ß-arrestins also act as ___ ____, binding to components of the ____  ____ machinery. Receptors are ____ via ___-___ ___
6.ß-arrestin ____from GPCR
7.Once internalized, GPCRs have two fates - ___ to the plasma membrane or ___.
 


1.Ligand binds to GPCR
2.G-proteins dissociate from GPCR
3.Desensitization of GPCRs begins with phosphorylation of agonist -occupied receptors by GPCR kinases (GRKs)
4.ß-arrestin binds to phosphorylated GPCRs, which sterically precludes coupling between the receptor and heterotrimeric G proteins
5.Receptor-bound ß-arrestins also act as adapter proteins, binding to components of the clathrin endocytic machinery. Receptors are endocytosed via clathrin-coated pits
6.ß-arrestin dissociates from GPCR
7.Once internalized, GPCRs have two fates - recycled to the plasma membrane or degraded●
 

12


Depending on the ___ subunit, GPCRs can activate ___ signaling pathways
•Originally classified based on their ability to ___ (Gαs) or ___ (Gαi) the enzyme___ ___ which converts____ to ____
•Currently subdivided into _ classes –  __ ___ ___ __ __ ___
•Different Gα  subunits activate different ____signaling pathway
•Gβγ also can ___ signaling pathways
 

Gi:___ AC: ____ cAMP

Gs: ___ AC: ___cAMP

Gq: activates ___: increase ___ ___ and ___

 

 


•Originally classified based on their ability to stimulate (Gαs) or inhibit (Gαi) the enzyme Adenylate cyclase, which converts ATP to cyclic AMP (cAMP)
•Currently subdivided into 6 classes – Gαs, Gαi, Golf, G0, Gq and G11/12
•Different Gα  subunits activate different effector-signaling pathway•
•Gβγ also can activate signaling pathways

 

Gi: inhibits AC: decrease cAMP

Gs: activates AC: increase cAMP

Gq: activates PLC: increase IP3 , DAD and cytoplasmic Ca

 


 

13


β1-Adrenergic Receptor Signaling


1.Binding of ____ or ____ to β1-adrenergic receptor
2.Activation of heterotrimeric _ proteins
3.____ of adenylate cyclase (AC) by ____
4.Adenylate cyclase converts ___ to ___
5.Activation of ______ by ____

Activated PKA can induce several signaling mechanisms

  - phosphorylation of___ (which can either activate or inactivate those enzymes)

  - Activate ___ ____ through phosphorylation

  - Activate______, which in turn ____ ____ – Negative

     Feedback

  - Activate ___ ____– change in protein synthesis

All of the above could contribute to changes in cellular ___ ___ , ___


1.Binding of norepinephrine or epinephrine to β1-adrenergic receptor
2.Activation of heterotrimeric G proteins
3.Activation of adenylate cyclase (AC) by Gαs
4.Adenylate cyclase converts ATP to cyclic AMP (cAMP)
5.Activation of protein kinase A (PKA) by cAMP

Activated PKA can induce several signaling mechanisms

  - phosphorylation of enzymes (which can either activate or inactivate those enzymes)

  - Activate ion channels through phosphorylation

  - Activate phosphodiesterase E (PDE), which in turn degrades cAMP – Negative

     Feedback

  - Activate transcription factors – change in protein synthesis

All of the above could contribute to changes in cellular function, morphology, growth etc

 

14


α1-Adrenergic Receptor Signaling


•Binding of ___ or ____ to α1 adrenergic receptor causes activation of heterotrimeric _ proteins.
•Activated ___ with ___bound activates its downstream target _____
•Activated PLC hydrolyzes the membrane____ _____producing ___ and ___
•IP3 binds to  and ____ a ___ ___ on ___, releasing calcium stores from inside the ER into the ____
•Calcium alters many cellular processes, in part by binding to ___ ____such as____
•The interaction of both ___and ___ with _____ activates its ____ activity and the phosphorylation of many different protein targets alters their activity. 
 


•Binding of norepinephrine or epinephrine to α1 adrenergic receptor causes activation of heterotrimeric G proteins.
•Activated Gq with GTP bound activates its downstream target phospholipase C (PLC)
•Activated PLC hydrolyzes the membrane lipid Phosphatidylinositol 4,5-bisphosphate (PIP2), producing inositol triphosphate (IP3) and diacylglycerol (DAG).
•IP3 binds to and opens a calcium channel on ER, releasing calcium stores from inside the ER into the cytoplasm.
•Calcium alters many cellular processes, in part by binding to regulatory proteins such as calmodulin.
•The interaction of both DAG and calcium with protein kinase C (PKC) activates its kinase activity and the phosphorylation of many different protein targets alters their activity. 
 

15


Receptor Tyrosine Kinases (RTKs)


•RTKs are_____proteins with their ligand-binding domain on the outer surface of the plasma membrane.

•Instead of having a cytosolic domain that associates with a trimeric G protein, however, cytosolic domain RTKs has an ____ ____ ___
•Whereas a GPCR has seven transmembrane segments, each subunit of a RTK usually has only ___ but ___ after binding ligands

•Bind ____ ligands which are ____
-___ ___ ____ (____, ___ ____)
-___ ____ (____)
-___ ___ ___ ____ ____ (___)
 


•RTKs are transmembrane proteins with their ligand-binding domain on the outer surface of the plasma membrane.

•Instead of having a cytosolic domain that associates with a trimeric G protein, however, cytosolic domain RTKs has an intrinsic enzyme activity

•Whereas a GPCR has seven transmembrane segments, each subunit of a RTK usually has only one but dimerize after binding ligands

•Bind diverse ligands which are proteins
-Secreted growth factors (epidermal growth factor, platelet-derived growth factor)
-Secreted hormones (insulin)
-Cell surface-bound signal proteins (ephrin)
 

•RTKs can be classified into 7 structural subfamilies (in mammals), each dedicated to its complementary family of protein ligands

16

RTKS are ___ too!

But all have

___
___
____

RTKS are diverse too!

But all have

EC ligand binding domain

tm helix

intracellular Y kinase domain

17

Activation of RTK

Inactive: ____

____s-->___-->____->____--> ______

__ ___ residues on IC side

__________ themselves

P groups serve as ___ ___ for ___ ___ ___ to attach and induce signal transduction

Each Phosphate group is ___ site for a diff downstream protein

Inactive: monomers

Ligan Binds-->Conf Change-->Dimerize-->Conf Change--> Activates kinase activity

6 Y residues on IC side

Autocrossphophorylate themselves

P groups serve as docking sites for downstream effector proteins to attach and induce signal transduction

Each Phosphate group is unique site for a diff downstream protein

18

Epidermal growth factor receptor – MAPK signaling

Signal transduction by growth factor receptors involves several steps

1.Binding of ___ ___ such as epidermal growth factor to cell surface receptors
2.Ligand binding causes ___ ___ in the receptor resulting in _____ of the receptor
3.Adapter proteins such as ____ bind to _____ ____

4.   Grb2 ____ ____ to the vicinity of the small ____ ____

5.Binding of ___ to ___ stimulates ___ ____ resulting in_________________.Binding of GTP causes __ ___ in ___ and ___ __

6.   Activated Ras ___ ___to the plasma membrane. Raf activates the ____________ – leading to immediate cellular changes and/or transcriptional changes

Signal transduction by growth factor receptors involves several steps

1.Binding of growth factors such as epidermal growth factor to cell surface receptors
2.Ligand binding causes conformational changes in the receptor resulting in autophosphorylation of the receptor
3.Adapter proteins such as Grb2 bind to phosphorylated RTK

4.   Grb2 recruits guanine nucleotide exchange factors (GEFs) to the vicinity of the small GTPase  

       Ras

5.Binding of SOS to Ras stimulates conformational changes resulting in the release of GDP and binding of GTP. Binding of GTP causes conformational changes in Ras and activates it

6.   Activated Ras recruits Raf to the plasma membrane. Raf activates the mitogen activated 

      protein kinase (MAPK) pathway – leading to immediate cellular changes and/or

      transcriptional changes

19

Example of RTK – Insulin receptor signaling

•Unlike growth factor receptors, insulin receptor exists in the membrane as preformed ____, with each half containing an __ and ___ ____

•Once insulin binds to the ___ subunits, the ___ subunits____ ___ ___.

_____________binds to ____ ____

•Receptor ____ ____ at multiple sites creating multipl___ ____ for different proteins•

•The downstream pathways activated are very similar to those activated by EGFR (____ ____ ____ ___).

•Unlike growth factor receptors, insulin receptor exists in the membrane as preformed dimers, with each half containing an α and β subunits.

•Once insulin binds to the α subunits, the β subunits autophosphorylate each other

•Insulin receptor substrate (IRS) binds to phosphorylated receptor

•Receptor phosphorylates IRS at multiple sites creating multiple binding sites for different proteins

•The downstream pathways activated are very similar to those activated by EGFR (RAS/MAPK, PI3K, PLC).

20

Example of RTK – Insulin receptor signaling

21


Intracellular Receptors

•Also known as ___ ____

•Signaling process begins with ___ of lipid soluble ligand across the plasma membrane

•Receptors are often complexed with an ___ to ___ ___ ___ ___.

Ligand binding usually activates the receptors by inducing a ___ ___, which allows __ ___ and subsequent __ __

•Consists of ___ receptor groups:

(1)those that bind ___ ligands - receptors are ___ ___ ___ with ___  ____ ligands, such as ___ ___ ___ ___

(2)those that bind ____l ligands - ___ ___ and ___ ___ ___

(3)those with __ ___ ligand – ___ ___, ___ component of the nuclear receptor superfamily

•Also known as nuclear receptors

•Signaling process begins with passage of lipid soluble ligand across the plasma membrane

•Receptors are often complexed with an inhibitor to prevent ligand-independent activation. Ligand binding usually activates the receptors by inducing a conformational change, which allows DNA binding and subsequent transcriptional regulation

•Consists of three receptor groups:

(1)those that bind steroidal ligands - receptors are gene transcription factors with known steroidal ligands, such as corticostreroids, estrogen, progesterone, and androgens

(2)those that bind nonsteroidal ligands - thyroid hormone and retinoic acid receptors

(3)those with no known ligand – orphan receptors, largest component of the nuclear receptor superfamily

22


Structure of Nuclear Receptors


•The N terminus of the NR called the ____ or ___ domain has ______ activity, is ___ ____ (ie. constitutively functional),____ ___ between receptors and is thought to be responsible for the ___ ___ ___.

•The  ____ ___ ____ (__) or the C domain is composed of two zinc fingers and is the ___ ____region within the NR superfamily


•The D or ___ domain allows for c___ ____s in the ___ structure following ___ ___

____ ___ ____ ( ____ ) or E/F domain ____ between NRs. Composed of 11-13 a-helices organized around a ____ binding pocket. LBDs also contain ___ ___ ____ and ___ ___ ___

•F domain is required for___ ___ ____


•The N terminus of the NR called the hypervariable or A/B domain has transactivation activity, is ligand-independent (ie. constitutively functional), highly variable between receptors and is thought to be responsible for the receptor-specific effects

•The DNA binding domain (DBD) or the C domain is composed of two zinc fingers and is the most conserved region within the NR superfamily


•The D or hinge domain allows for conformational changes in the protein structure following ligand binding.

•The ligand binding domain (LBD) or E/F domain varies between NRs. Composed of 11-13 a-helices organized around a hydrophobic binding pocket. LBDs also contain nuclear localization signals and protein interaction motifs.

•F domain is required for ligand-dependent activation. 

23


Activation of Nuclear Receptors 

•NRs are mostly found in the ____,  masked by ____ proteins such as heat shock proteins (HSP), which ___ __ ___

•When the ligand binds, HSP ___, receptor ____, translocates to the ____, and binds to s___ ___ ____ known as the ___ ___ ___

•The NR-DNA complex ____ other cofactors required for ____ and target gene is transcribed and then translated

•NRs are mostly found in the cytosol, masked by chaperon proteins such as heat shock proteins (HSP), which prevents self activation

•When the ligand binds, HSP dissociates, receptor dimerizes, translocates to the nucleus, and binds to specific DNA sequences known as the hormone response element (HRE)

•The NR-DNA complex recruits other cofactors required for transcription and target gene is transcribed and then translated

24


Signal Termination


•Signals are terminated by various means

1.Termination of the ___ ____ itself

  ex – polypeptide hormones like insulin are taken up by cells of liver and degraded.

       - acetylcholine is degraded in the synapse by acetylcholine esterase

2.____of receptors through ____, ____ and____
3._____ of GTP to GDP of G proteins
4.____ of ___ ____

  ex – degradation of cAMP by PDE

5.    ___ of ____groups by phosphatases

25


Signaling pathways cross-talk

Therefore, modifying one pathway will not only affect that pathway but could have a ___ __ on several pathways


Signaling pathways cross-talk

Therefore, modifying one pathway will not only affect that pathway but could have a global effect on several pathways