Cytokines are a diverse group of secreted factors
regulating cellular growth and differentiation.
Knowledge of cytokine signaling has exponentially
increased over the past few years. This
chapter focuses on only two structurally related
families of cytokine receptors, Type I and Type
II receptor families, since their receptor phosphorylation
leads to the activation of the Stat
family of transcription factors. Members of these
two receptor families have no intrinsic tyrosine
kinase activity and utilize Janus kinases (Jaks)
to initiate intracellular signaling. Type I receptors
bind hormones such as erythropoietin,
thrombopoietin, prolactin, growth hormone,
and specific interleukins, while Type II receptors
bind interferons (IFN). The structure and function
of various Jaks and Stats are the focus of
this review; the latter in particular are emphasized
in accordance with the transcription factor
theme of this book. Since many interleukins are
important in lymphoid development and immunoregulation,
the critical roles that Jaks and
Stats play in cytokine signaling may best be
illustrated in the context of lessons from human
disorders resulting from Jak mutations and the
study of Jak/Stat deficient mice. The space constraint
in this review makes citation of all of the
studies contributing to the understanding of
Jaks and Stats an impossible task. Hence,
readers interested in more information are directed
to some excellent reviews on this subject:
Aringer et al., 1999; Bach et al., 1997; Baird et
al., 1999; Carter-Su and Smit, 1998; Darnell et
al., 1994; Hoey and Grusby, 1999; Ihle, 1995;
Ihle et al., 1998; Leonard and O’Shea, 1998;
O’Shea, 1997.
An important caveat should be made first,
however. The fact that much work has focused
on the role of Jaks and Stats in cytokine signaling
has led to the notion of a ‘‘Jak-Stat’’ pathway.
While it has been useful to think of signaling in
these terms and genetic data on Drosophila can
be interpreted as a linear pathway, such a simplistic
view of mammalian Jak-Stat systems can be
misleading, as is elaborated below