IL-7 signaling in T lymphocytes
Interleukin-7 (IL-7) is an essential cytokine for
proliferation, maintenance and survival of T-lymphocytes .
IL-7 receptor activates pathways that regulate lymphocyte
survival, glucose uptake, proliferation and differentiation .
IL-7 receptor consists of the IL-7 receptor alpha chain
(IL7RA) and the common cytokine gamma chain
(IL-2R gamma chain) .
IL-7 ligation to the IL-7
receptor stimulates the trans-phosphorylation of receptor associated Janus
kinases 1 and 3 (JAK1 and
JAK3), which in turn phosphorylate tyrosine residues on the
receptors themselves , , .
IL-7 receptor serves as docking sites for SH2 domain
proteins including the Signal transducers and activators of transcription family of
transcription factors (STAT1,
STAT3, STAT5 and
STAT6) which are activated by JAK-mediated phosphorylation
, . STAT5 promotes
transcription of B-cell CLL/lymphoma 2 (Bcl-2) stimulating
cell survival . STAT5 promotes transcription
of Suppressor of cytokine signaling 1 (SOCS1) inducing
negative feed-back on IL-7 signaling , .
IL-7 receptor induces JAKs/
PTK2B protein tyrosine kinase 2 beta (Pyk2(FAK2)) cascade
that participates in activation of T cell survival .
Activated IL-7 receptor stimulates
Phosphatidylinositol 3-kinase (PI3K)/ V-akt
murine thymoma viral oncogene (AKT/PKB) cascade via
JAKs/ Insulin receptor substrates 1 and 2
(IRS-1, IRS-2) ,  and/or Src family kinases FYN oncogene related to SRC
(Fyn) and Lymphocyte-specific protein tyrosine kinase
(Lck) , . Activated
PI3K induces conversion from
Phosphatidyl-4,5-inositol bisphosphate (PtdIns(4,5)P2) to
Phosphatidyl-3,4,5-inositol triphosphate (PtdIns(3,4,5)P3).
PtdIns(3,4,5)P3 in turn induces
AKT/PKB and 3-phosphoinositide dependent protein kinase-1
(PDK (PDPK1)) activation that promotes T lymphocytes
proliferation and survival , .
AKT/PKB complex induces Solute carrier family 2 member 1
(GLUT1) activation inhibition of transcriptional factor
Forkhead box O3 (FOXO3A). GLUT1
stimulates Glucose uptake thus promoting cell survival
IL-7 stimulates V(D)J recombination of T-cell receptor
gamma chain (TCR gamma locus) in T cells. V(D)J
recombination is assemblage of mature genes encoding the component chains of TCR and
immunoglobulin proteins from germ-line arrays of variable (V), diversity (D), and joining
(J) gene segments during lymphoid development , .
STAT5 plays a key role in synthesis and V(D)J recombination
of TCR gamma locus with participation of histone acetylases
p300 and CBP .
It is possibly, that AKT/PKB-dependent inhibition Forkhead
box O1 (FKHR) stimulates
Recombination activating gene 1 and 2 (RAG1
and RAG2) transcription, thus inducing V(D)J
recombination of TCR gamma locus. The
RAG1/ RAG2 dimer recognizes the
synapsis formed by the recognition motifs and initiates the cleavage step of V(D)J
recombination , , .
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