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JAK-STAT Pathway PDF
JAK-STAT Pathway PDF
JAK-STAT Pathway PDF
The JAK/STAT signaling and growth factors. JAK activation Mechanistically, JAK/STAT signaling is
stimulates cell proliferation, relatively simple, with only a few
pathway differentiation, cell migration and principal components (for reviews, see
Jason S. Rawlings, Kristin M. apoptosis. These cellular events are Aaronson and Horvath, 2002; Heinrich
Rosler and Douglas A. Harrison* critical to hematopoiesis, immune et al., 2003; Kisseleva et al., 2002;
development, mammary gland O’Shea et al., 2002). As described
University of Kentucky, Department of Biology, 101
T.H. Morgan Bldg., Lexington, KY 40506, USA development and lactation, adipogenesis, above, a variety of ligands and their
*Author for correspondence (e-mail: sexually dimorphic growth and other receptors stimulate the JAK/STAT
dough@uky.edu) processes. Predictably, mutations that pathway. Intracellular activation occurs
reduce JAK/STAT pathway activity when ligand binding induces the
Journal of Cell Science 117, 1281-1283
Published by The Company of Biologists 2004
affect these processes (reviewed by multimerization of receptor subunits.
doi:10.1242/jcs.00963 Igaz et al., 2001; O’Shea et al., For some ligands, such as erythropoietin
2002). Conversely, mutations that and growth hormone, the receptor
The Janus kinase/signal transducers and constitutively activate or fail to regulate subunits are bound as homodimers
activators of transcription (JAK/STAT) JAK signaling properly cause while, for others, such as interferons and
pathway is one of a handful of inflammatory disease, erythrocytosis, interleukins, the receptor subunits are
pleiotropic cascades used to transduce a gigantism and an array of leukemias. heteromultimers. For signal propagation
multitude of signals for development and Here we present a general overview of through either homodimers or
homeostasis in animals, from humans the JAK/STAT pathway and illustrate heteromultimers, the cytoplasmic
to flies. In mammals, the JAK/STAT the primary mechanisms of activation domains of two receptor subunits must
pathway is the principal signaling and regulation of this essential signaling be associated with JAK tyrosine kinases.
mechanism for a wide array of cytokines cascade. JAKs are distinctive in that they have
JAK-binding
receptors
Transmembrane
domain LIG
jcs.biologists.org
JAK Box 1
Activation Inactivation
{
binding Box 2
LIG RTKs
Phosphorylation Y
target/docking site
SH2-B
SH2-B JAK
JAK P-Y
Y JAK Y-P
P
Src JAK Y-P
P
AK P
P-Y JAK Y-P SOCS P
P-Y JAK
Y-P
Y-P
Y-P
P SHP-1
P-Y
StIP Y-P AdPs GRB2 GRB2 P-Y
Y P-Y Y-P BC
STAM STAT SHP-1
T P-Y
STAT SOCS P-Y
SOCS P-Y
YP
Y-P (SHP-2,
HP 2 Y-P
Y-P
P
SOS
Shc, etc.) SHP-1 BC Ub
b
MEK
S-P ((ERK1/2, p38, JNK, iga ds Many (below) 2-3 ( pd, Upd , U d2?) 0 0 SAP Zn-RF S/T
Oligomerization DNA-binding Transcriptional Rec pto s Many (below) 1-2 (Dome, C 14 25?) 0 0
domain domain activation domain PKCδ, FRAP) 4 Serine/threonine-rich
SAP domain RING finger
Coiled coil Phosphotyrosine s 7 (STA TAT6) 1 3 ( -c) (target binding) domain
binding (recruitment domain (target binding)
(protein interaction)
and dimerization)
NPI-1 Ran S 8 o ) (SUMO transfer)
In ro s s GP Rs