Transduccion 2008
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Transcript of Transduccion 2008
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Transducción de SeñalesTransducción de Señales
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Señal (hormona)
canal iónico Receptor (7 regiones transmembrana)GABA A - NMDA (tirosina quinasa)
T d t (P t í G)Transductor (Proteína G)
Amplificador (PLC, Adenilato ciclasa)
Segundos Mensajeros
cAMP
IP3
Ca2+
(flujos iónicos) Efectores (expresión génica)
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Señales extracelulares
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Señal: Catecolaminas
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Señal: Esteroides
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Señal:Eicosanoides
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Receptores
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Receptores Ionotrópicos
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Receptores con Actividad Enzimática Intrínsecap
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Tirosina Quinasa
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Receptores Asociados a TirosinaReceptores Asociados a Tirosina--QuinasaQuinasa
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Receptor y transductor G
RLH – G protein complexRLH G protein complex
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Transductores
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FRET: Fluorescent Resonance Energy TransferResonance Energy Transfer
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Transductor pequeño y móvil
Proteínas G pequeñas (Small GTP binding proteins)Proteínas G-pequeñas (Small GTP-binding proteins)
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Proteínas G-pequeñas (Small GTP-binding proteins)
Factores de Iniciación y elongación (sintesis de proteínas).Ras (Cascadas de factores de crecimiento)Rab (Direccionamiento y fusión de Vesículas)ARF (F ió d í l bi t )ARF (Formación de vesículas cubiertas).Ran (Transporte de proteínas dentro/fuera del nucleo)Rho (Regulación del citoesqueleto de actina)Rho (Regulación del citoesqueleto de actina)
Todas las proteínas G-pequeñas difieren en su estadoconformacional dependiendo si es GDP o GTP elnucleótido presente en su sitio de unión Generlmente GTPnucleótido presente en su sitio de unión. Generlmente GTPinduce el estado activado.
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AmplificadoresAmplificadores
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Señal: Catecolaminas
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Receptor
Transductor
AmplificadorAmplificador
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NN
ATP
NH2
NNO
P
O O
O
HO
OPP
ATP
3'
5'
HO OH
NH 2
..
Adenilato ciclasa
N
N
N
NOO
2
O
cAMP
P
O O 3'OH
cAMP fosfodiesterasa
N
N
N
N
NH
OO
2
O
cAMP fosfodiesterasa
5'-AMP
O
P
OHO
O
3'
O
OHO
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Amplificación de señal por PLC
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Amplificación de señal por PLC
Segundos mensajeros
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EfectoresEfectores
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Proteina kinasa activada por AMPc (PKA)
AMPc Subunidad regulatoria
Subunidad cataliticaActividad Kinasa
g
PKA’s regulatory subunit (green and red) through a molecular spring (light blue, right).U d t i (l t f th fi ) th i l d t h i th l tUnder tension (lower part of the figure) the spring leads to a change in the regulatorysubunit which causes the catalytic subunit (purple, left) to separate, activating theenzyme. Giovanni Zocchi/UCLA Physics.
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OProtein Kinasekinasa
Protein OH + ATP Protein O P O−
O−
+ ADP
Protein Kinase
kinasa
OPi H2O
Protein Phosphatasefosfatasa
Una proteina quinasa transfiere el fosfato terminal del
Protein Phosphatasefosfatasa
Una proteina quinasa transfiere el fosfato terminal delATP a un radical hidroxilo (-OH) de un aminoácidoparticular en la proteína.
Una fosfatasa cataliza la remoción del Pi por hidrólisis.
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Aminoácidos Polares sin CargaR con Grupos -OHR con Grupos OH
• Serina (Ser S) y Treonina (Thr T) tienen cadenasSerina (Ser, S) y Treonina (Thr, T) tienen cadenas polares no cargadas
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A i á id A á iAminoácidos Aromáticos
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PKCs
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Vías de señalización(Pathways)
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MAPKinasas
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Vía de EGF
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Señal:Eicosanoides
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Señal: Esteroides
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EsteroidesAdrenales
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EsteroidesSexuales
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Receptor de estrógeno unido al DNA
Ef t ó iEfectos genómicos
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Variabilidad de señales externas y treceptores
V/sLimitadas señales intracelulares
(Crosstalk )
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Antecedentes
La esteroidogénesisaguda requiere laactivación de 2 víastransduccionalestransduccionales
PKA y PKC
MA-10
Leydig ratón
Jo Y, King SR, Khan SA, Stocco DM.Involvement of protein kinase C and cyclic adenosine 3',5'-monophosphate-dependent kinase insteroidogenic acute regulatory protein expression and steroid biosynthesis in Leydig cells. Biol Reprod. 2005 Aug;73(2):244-55
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Segundos Mensajeros