INTRACELLULAR COMUNICATION II

Aloa Lamarca Dams

16/10/2012

SECOND MESSENGERS

Ligand Receptor Receptor activation leads to second messenger activation.

2.2-Second messengers properties:

Short half live. They are generated when they are necessary, and once the function is done, they are degraded. Small molecules, with a low molecular weight.

AMPc GMPc DAG 2-Type of second messengers

IP3
Ca2+

Phosphoinositols (PLC, PKC...)

2.1- AMP cyclic: SINTHESIS AND DEGRADATION

ATP AMPc AMP

2n messenger AMPc is the most common second messenger in animal cells.

AMPc increase, in response to an extracellular stimul

Brian J et al, Science 1993

Role of AMPc in the cell

Glycolisi Lipogenesis Gluconeogenesis Muscular contraction

Learning process

Diferentiation

AMPc
Apoptosis

Ionic transport

Growth control Membrane secretion

Mechanism of action of AMPc

Hormones bind receptors, and membrane-bound adenylyl cyclase is activated via the G protein Adenylyl cyclase catalyzes the conversion of ATP to cAMP cAMP activates protein kinases Protein kinases catalyze the phosphorylation of a specific protein, which triggers a chain of reactions leading to the particular metabolic effect of the hormone Protein kinases are very specific in action cAMP is rapidly inactivated and converted to AMP

ACTIVATION OF PKA BY AMPc

AMPc Kinases activation

1- Canvis en la interacci amb altres protenes (reguladores /substrats) 2- Alterant lactivitat cataltica 3- Provocant canvis en la localitzaci de lenzim

- PKA Catalytic activity: Serine/Threonine Kinase - PKA target motif:

X-Arg/Lys X Ser/Thr hydrophobic aa

Phosphate
[Figura 13-19 / Cooper, GM. The Cell]

ACTIVATION OF CREB BY AMPc

http://www.youtube.com/watch?v=iGb93jCKVXs&feature=related

A clinic example:

2.2-GMP cyclic: SINTHESIS AND DEGRADATION

Phosphodiesterase

GMP

GMPc

Clinic example: VIAGRA

2.3- IP3 - DAG

IP3 - DAG

IP3 and DAG with more detail:

http://www.youtube.com/watch?v=ejq99wLEMTw&feature=related

Clinic example

The Fight or Fly response

http://www.youtube.com/watch?v=4g25d7_Afmc&feature=related

Hi ha un increment del glucogen. Hipoglucemies severes

Hi ha un increment del glucogen en vacuoles.

No sallibera lactat durant lexercici

Calcium
Calcium entry can occur in response to a G-protein stimulated event The calcium may bind CaM and activate a protein kinase that may go on to regulate other cellular events

CALCIUM CALMODULIN COMPLEX

CaM-Kinases activation by Ca-Calmodulin complex:

Calmodulin in PARKINSON AND ALZHEIMER DISEASE

NMDA RECEPTORS CAMK Parkinson Desease