Activation of Stat5 by interleukin 2 requires a carboxyl-terminal region of the interleukin 2 receptor beta chain but is not essential for the proliferative signal transmission.

Abstract

The high-affinity interleukin 2 (IL-2)

Cell type-specific roles of Jak3 in IL-2-induced proliferative signal transduction

“…Two members of the Jak kinase family protein tyrosine kinases, Jak1 and Jak3, are associated with IL-2Rβ and γc, respectively, and activated upon IL-2 stimulation [6][7][8]. Activation of Jak1 and Jak3 induces activation of Stat5/Stat3 and other signaling pathways to initiate cell proliferation [9][10][11]. Although IL-2 can transmit signals in IL-2R-reconstituted fibroblast cell lines [12,13], they do not proliferate in response to IL-2.…”

Signalling by the oncogenic receptor tyrosine kinase Xmrk leads to activation of STAT5 in Xiphophorus melanoma

“…Although a variety of studies attempted to de®ne the role of STAT5 in cell growth and di erentiation, its requirement for such processes is still a subject of dispute. Some data describe an implication of STAT5 in the control of proliferation (Damen et al, 1995;Friedmann et al, 1996;Mellitzer et al, 1996), whereas others show that receptor mutants lacking the ability to activate STAT5 are still able to transduce mitogenic signals (Quelle et al, 1996;Fujii et al, 1995). Moreover, while a dominant negative STAT5 protein was found to inhibit IL-3 driven DNA synthesis in Ba/F3 cells (Mui et al, 1996), the expression of another dominant negative STAT5 had no e ect on IL3-induced proliferation in myeloid cells .…”

The role of Stat5a and Stat5b in signaling by IL-2 family cytokines

“…Like most type I cytokine receptors, the cytoplasmic domains of both IL-2Rb and g c contain certain structural features, including`Box1/Box2' regions for binding JAK kinases, and a number of tyrosine residues (Bazan, 1990;Leonard and O'Shea, 1998). At least in the case of IL-2Rb, phosphorylation of some of these tyrosine residues creates docking sites for the recruitment of signaling molecules (Friedmann et al, 1996;Fujii et al, 1995;Goldsmith et al, 1995;Ravichandran and Burako , 1994). In contrast, IL-2Ra has a short cytoplasmic domain (only 13 amino acids); it mainly contributes to IL-2 binding a nity and is unlikely to contribute to signaling per se (Leonard et al, 1984;Nikaido et al, 1984).…”

“…Jak3 plays a critical role in activation of Stat5 proteins by IL-2 IL-2 activates both Stat5a and Stat5b in normal T lymphocytes (Fujii et al, 1995;Ga en et al, 1995;Hou et al, 1995;Lin et al, 1995) and NK cells (Yu et al, 1996). The importance of Stat5 activation in IL-2 signaling was ®rst suggested by transfection experiments using either deletion or other mutated forms of IL-2Rb.…”