Dra.

Luz Marina Guerrero Espino

 COMUNICACION INTER-
INTRACELULAR
Extracelular
Modulador

Receptor

Transductor

Intracelular Amplificador

2do Mensajero

Efector interno
RECEPTORES son proteínas de membrana
Excepto los receptores de las hormonas esteroideas y tiroideas que son proteínas
citoplasmáticas
Algunos receptores son canales iónicos operados por ligando
Algunos receptores producen segundos mensajeros mediante una proteína G

gamma gamma
alfa GTP alfa GTP
beta beta
GDP
alfa

AMPc IP3
Algunos receptores tienen actividad proteín kinasa

P P

P
Los receptores de las hormonas esteroideas y tiroideas se unen al DNA
MUTACIONES EN UN RECEPTOR

Síndrome de Laron

Mutación en el gen del receptor de la hormona del crecimiento

La hormona de crecimiento está elevada pero no tiene

efecto
ALTERACIONES EN LOS MECANISMOS POSTRECEPTOR

Osteodistrofia heriditaria de Albright's

Mutación en la subunidad alfa de la proteína G

La hormona paratiroidea está elevada pero no tiene
efecto
RESPUESTA CRUZADA ENTRE RECEPTORES

El exceso de hormona de crecimiento produce gigantismo, y

también secreción de leche (galactorrea)

La hormona del crecimiento puede actuar en el receptor de la prolactina

Hormona de crecimiento prolactina

ANTICUERPOS CONTRA RECEPTORES: INHIBIDORES

Miastenia gravis

Se producen autoanticuerpos contra el receptor de la acetilcolina en el

músculo
ANTICUERPOS CONTRA RECEPTORES: ESTIMULADORES

Enfermedad de Graves

Se producen autoanticuerpos contra el receptor de la hormona TSH en

el tiroides, que lo estimulan como si fuera el ligando
RUTAS DE TRANSDUCCION
CELULAR
1ra ruta
I ° ° MENSAJERO
 2da ruta 3ra ruta
I ° MENSAJERO I ° MENSAJERO

RECEPTOR RECEPTOR RECEPTOR

AMPc (2do. Mensaj.) GMPc DAG - IP3

Ca

Protein Kinasa A Protein kinasa G Protein Kinasa C

Efector interno Efector interno Efector interno

 EFECTORES
INTERNOS

 Serina-treonina kinasas

 Tirosina-kinasas
EGF Signaling Pathway
Cascadas de señales MAP kinas
 The MAPK/Erk signaling cascade
is activated by a wide variety of
receptors involved in growth and
differentiation including receptor
tyrosine kinases (RTKs), integrins,


and ion channels. The specific
components of the cascade vary
greatly among different stimuli, but
the architecture of the pathway
usually includes a set of adaptors
(Shc, GRB2, Crk, etc.) linking the
receptor to a guanine nucleotide
exchange factor (Sos, C3G, etc.)
transducing the signal to small
GTP binding proteins (Ras, Rap1),
which in turn activate the core unit
of the cascade composed of a
MAPKKK (Raf), a MAPKK (MEK1/2)
and MAPK (Erk). An activated Erk
dimer can regulate targets in the
cytosol and also translocate to the
nucleus where it phosphorylates a
variety of transcription factors
regulating gene expression.

http://www.cellsignal.com/ref
erence/pathway/MAPKERK.
asp ACCESADO 4-07--05
G-protein-coupled receptors
(GPCRs) are activated by a
wide variety of external stimuli.
Upon receptor activation the G-
protein exchanges GDP for
GTP, causing the dissociation of
the GTP-bound Galpha and the
Gbetagamma subunits,
triggering diverse signaling
cascades. Receptors coupled to
different heterotrimeric G-
protein subtypes can utilize
different scaffolds to activate
the small G-protein/ MAPK
cascade, employing at least
three different classes of
tyrosine kinases. Src family
kinases are recruited following
activation of PI3Kgamma by
Gbetagamma subunits. They
are also recruited by receptor
internalization, cross-activation
of receptor tyrosine kinases, or
by signaling through an integrin
scaffold involving Pyk2 and/or
FAK. GPCRs can also employ
PLCbeta to mediate activation
of PKC and CaMKII, which can
have either stimulatory or
inhibitory consequences for the
downstream MAPK pathway.
Ceramide Signaling Pathway
http://www.biocarta.com/pathfiles/h_ceramidePathway.asp, accesado
4-07-05
• Serina-treonina kinasas

• Tirosina-kinasas

EFECTORES INTERNOS
EGF Signaling Pathway
Cascadas de señales MAP kinas
The MAPK/Erk signaling cascade
is activated by a wide variety of
receptors involved in growth and
differentiation including receptor
tyrosine kinases (RTKs), integrins,
and ion channels. The specific
components of the cascade vary
greatly among different stimuli, but
the architecture of the pathway
usually includes a set of adaptors
(Shc, GRB2, Crk, etc.) linking the
receptor to a guanine nucleotide
exchange factor (Sos, C3G, etc.)
transducing the signal to small
GTP binding proteins (Ras, Rap1),
which in turn activate the core unit
of the cascade composed of a
MAPKKK (Raf), a MAPKK (MEK1/2)
and MAPK (Erk). An activated Erk
dimer can regulate targets in the
cytosol and also translocate to the
nucleus where it phosphorylates a
variety of transcription factors
regulating gene expression.

http://www.cellsignal.com/ref
erence/pathway/MAPKERK.
asp ACCESADO 4-07--05
G-protein-coupled receptors
(GPCRs) are activated by a
wide variety of external
stimuli. Upon receptor
activation the G-protein
exchanges GDP for GTP,
causing the dissociation of
the GTP-bound Galpha and
the Gbetagamma subunits,
triggering diverse signaling
cascades. Receptors coupled
to different heterotrimeric G-
protein subtypes can utilize
different scaffolds to activate
the small G-protein/ MAPK
cascade, employing at least
three different classes of
tyrosine kinases. Src family
kinases are recruited
following activation of
PI3Kgamma by Gbetagamma
subunits. They are also
recruited by receptor
internalization, cross-
activation of receptor
tyrosine kinases, or by
signaling through an integrin
scaffold involving Pyk2
and/or FAK. GPCRs can also
employ PLCbeta to mediate
activation of PKC and
CaMKII, which can have
either stimulatory or
inhibitory consequences for
the downstream MAPK
pathway.
Ceramide Signaling Pathway
http://www.biocarta.com/pathfiles/h_ceramidePathway.asp, accesado
4-07-05
Las mutaciones activadoras en protooncogenes
generan oncogenes

Estos genes mutados (oncogenes) originan

proteínas defectuosas que alteran el crecimiento
celular.

Factores de crecimiento producidos en exceso:

Sis PDGF.
Receptores de factores de crecimiento siempre
activos:
ErbB􀃆 EGFR.
Proteinas de transducción de señal
descontroladas:
- Proteínas G alteradas: Ras.
- Protein-quinasas (Tyr o Ser-Thr) alteradas:
Src, Raf.
Factores de transcripción alterados:
fos, jun,Myc, Ciclinas.
Ciclinas alteradas.
CANCER BUCAL
http://www.blc.arizona.edu/marty/411/Modules/mod19.html accesado 12-04
GRACIAS