Chapter 19

Ligands bind   at high affinity

Receptors are what time of molecule?

What are hormone types 1,2,and 3?

  refers to the post-R signaling cascade, signal propagation, effectors, transducers, second messengers and intracellular events initiated by   relayed to inside of cell

 involves the cell receiveing input from multiple sources and deciding how to respond

Cellular   involves how cell may respond by changingits cellular process. e.g. divide (proliferate), programmed cell death(apoptosis),send signals to other cells(secretion),etc.

  a molecule is secreted in one place, gets into the bloodstream and acts at a far away organ (receptor). Mainly hormones.

  a molecule is secreted by one cell and acts at a nearby target. Ex: presynaptic and post-synaptic neurotransmission

  a cell secreted a molecule that acts on the same cell (or on cells of thesame type). Example: growth factors

Receptors can be  , embedded in the , or  

What are the 4 main steps in signal transduction?
1. Secretion of  
2.   (molecule binds to receptor)
3. Signal   (receptor senses a interation with ligand, changes conformation, and activates secondary messengers)
4. Cell  

Transmembrane class receptors include  ,  , 

Upon prolonged stimulation, the receptors get   (even if  )

A G-protein receptor kinase (GRK) – the  of the receptor

The –P receptor binds with high affinity to  , which inactivates by preventing interaction with  

Arrestins are also adaptor prots that helps sequestration into  

There are mainly 3 types of G-proteins that associate with GPCRs:  ,  &  

The first messengers are for sending the  signal, the secondary messengers are important for signal  

Gq - Activates   at the inner portion of the cell membrane. PLC cleaves  , a lipid at the cell membrane, yielding   and  

G-protein coupled receptors use  , not  ! The high-energy molecule that associates with the alpha subunit is  , which gets hydrolyzed to  .

Both IP3 and DAG can act as  

IP3 is   and DAG remains
at the  

IP3 binds to   channels in the  and allows release of  

DAG interacts
and activates
 , which
then causes
further cellular
responses.

Gs activates  , which makes   from 

Gi inhibits  

After Gs activates adenyate cyclase, cAMPs bind to the repressor subunit of  . The  subunit of PKA then  other targets.  amplify the original signal (cascade). This is the mechanism used
by   receptors

Gi Provides   to  activation

 - one signal gets
amplified and affects many molecules
downstream

cAMPs gets inactivated by  

Coffee inhibits
  which leads to prolonged breakdown of
 

Activation of   - increase in intracellular calcium

Activation of  - releases smooth muscle contraction

Blocking   - release smooth muscle contraction

2 types of receptors directly
related to kinase activity

1. Receptors with   kinase activity
2. Receptors with   kinase activity

Kinases   a phosphoate, phosphotases   a phosphate

3 types of intrinsic kinase activity
1.  domain
2.   domain
3.  domain

2 subtypes of intrinsic kinase activity
1.   Kinases
2.   Kinases

Signal in response to ligands (growth factors, cytokines,
and hormones), several ligands can activate  

RTKs highly activate during  ,  ,  , and  

RTKs regulates   and  ,
 ,  .

RTKs common feature of this class of receptors is that
the   of the receptor is
activated when the ligand/hormone binds to the
 

The signal transduction pathway is propagated
 through   and recruitment
of signal transducers (also called .

Ras can activate 2
distinct branches of
RTK downstream
signaling:
(1 (2)  

Deregulation in either or both branches found in  and  

Hormones can be divided into 3
groups/classes based on their chemical structure: I.  , II.  , and III.  

Why is insulin hard to produce?

 are located within the cell and only available to
membrane diffusible, lipophilic ligands

  normally sit on the
DNA, inactivating gene expression

When thyroid binds, it displaces a  
from the receptor and allows binding of  , which promotes gene
 .

What are three examples of nuclear receptors?
1.  
2. 
3.  

Nuclear receptors bind to Bind to   in DNA

Thyroid hormones cause increase in 

The thyroid cells synthesize  , which contains a lot of  molecules.

In the addition of iodine thyroid hormine becomes, they become  or  .This is the form in which it is stored in the  

For liberation of T3 and T4,   is split off. Some   is transformed into   in the blood. Most  is therefore formed  

  - speeds up cell’s basal metabolic rate

Hyperthyroidism causes increased cardic output AKA  

  activates the sympathetic nervous system (fight or flight response)

Symptoms of   include weight loss, heat intolerance, rapid heart rate (tachycardia),
sweating, hyperactivity, anxiety, insomnia, eyes appear more open than normal

  results in too much thyroid hormonal stimulation

The main cause of hyperthyroidism is   (autoimmune disease)

The main symptoms of Grave's disease include