COMUNICACION

INTRACELULAR
Dr. Fredy Paredes
Villanueva

Dpto. de Fisiologa Humana

CITOCINA

FACTOR DE CRECIMIENTO

CINASA DE LA PI3

RECEPTORES CON
ACTIVIDAD INTRINSECA
TIROSINA CINASA

RECEPTOR SIN
ACTIVIDAD
INTRINSECA TIROSINA
CINASA

RECEPTOR DE 7 TRAMOS

PLC

JAK
VIA DE LA CINASA PI3

Akt

VIA DE LA CINASA MAP

ACTIVACION DEL RAS

FOSFORILASA DE
LA CINASA MAP

VIA DE LA IP3

LIBERACION DE IP3

VIA DEL AMPc

AMPc

VIA DEL JAK/STAT

LIBERACION DE CA 2+

STAT
ACTIVACION DEL FACTOR DE TRANSCRIPCION

RUTAS DE TRANSDUCCION CELULAR

1ra ruta

2da ruta

3ra ruta

I MENSAJERO

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

PROTEINA G

Es un transductor celular
Esta conformada por 3 subunidades:
alfa, beta y gamma
En reposo: GDP unido a la subunidad
alfa
En actividad: GTP desplaza al GDP y
se separa la subunidad alfa de las
subunidades beta y gamma

EFECTORES INTERNOS

Serina-treonina kinasas

Tirosina-kinasas

Kuala
Lumpur,
Malasia

EGF Signaling Pathway

Cascadas de seales 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/
reference/pathway/MAPKERK
asp

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 Gprotein 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,
crossactivation
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

Modificacin del Nmero de

Receptores

Regulacin homloga: up-down

regulation

Up-regulation: Insulina en diabetes m., EFG,

GH, LH, HCG, PRL
Down-regulation: Insulina en obesidad, ADH
en vasos

Regulacin heterloga: Insulina y GH, PRL

y LH, E2 y LH

Mode of Action of Estradiol

Estradiol
E

AF2

+ ER

Receptor
AF1 dimerization

Coactivator

AF1

Nuclear
localization of
fully active ER
to ERE

AF1 + AF2
ACTIVE

E=Estrogen.
ER=Estrogen receptor.
AF1=Activation function 1.
AF2=Activation function 2.
ERE=Estrogen response element.
RNA POLII=RNA polymerase II.

ERE

Coactivator

AF1 and AF2

recruit
coactivators

Wakeling AE, et al. Endocr Relat Cancer. 2000;7:17-28.

RNA
POLII

FULLY
ACTIVATED
TRANSCRIPTION
(tumor cell
division)

Las mutaciones activadoras en protooncogenes

generan oncogenes
Estos genes mutados (oncogenes) originan
protenas 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 transduccin de seal
descontroladas:
- Protenas G alteradas: Ras.
- Protein-quinasas (Tyr o Ser-Thr) alteradas:
Src, Raf.
Factores de transcripcin alterados:
fos, jun,Myc, Ciclinas.
Ciclinas alteradas.

http://www.blc.arizona.edu/marty/411/Modules/mod19.html accesado 12-04

GRACIAS !!!!!!!