Biology Reference
In-Depth Information
F i g u r e 14.2. Activation of the JAK/STAT pathway in HIV infection. In addition to a variety of
cytokines and growth factors that may be dysregulated by HIV infection, either virus replication or
viral proteins have been reported to regulate the expression and/or the activation of this important
signal trasnduction pathway (Bovolenta et al., 1999a; Pericle et al., 1998). Interaction of the HIV
gp120/160 Env with CD4 and/or the chemokine receptor has been shown to lead to the activation
of Ca
¯uxes and/or focal adhesion kinase Pyk2 (Arthos et al., 2000; Cicala et al., 2000; Davis et
al., 1997; Popik and Pitha, 1998; Popik et al., 1998; Selliah and Finkel, 1998; Weissman et al.,
1997).
IL-2: A KEY CYTOKINE IN HIV INFECTION
IL-2 deserves a speci®c place in the study of HIV infection for its multiple e¨ect
exerted in vitro, but in particular for its potential of becoming a therapeutic
tool for the long-term therapy of infected individuals. IL-2 induces the prolif-
eration and activation of T lymphocytes via heterodimerization of the common
b and g chains of the receptor, whose cytoplasmic tails are critical for trans-
duction of the IL-2 mediated signal, and association of the a chain that in-
creases the a½nity of the receptor for the cytokine (Waldmann, 2000). Binding
of IL-2 to its own receptor leads to the recruitment and activation of JAK1 and
JAK3 to b and g chains. Transduction of proliferative signal requires JAK3
activity, whereas a JAK3-independent signaling pathway prevents apoptosis
and involves various nonreceptor-type tyrosine kinases, such as p56(lck) and
other Src family proteins ( Waldmann, 2000). However, activation of p56(lck)
alone is insu½cient for transducing proliferative signals and, therefore, acts in
concert with JAK3-mediated receptor activation. In addition, it has been dem-
