Protein tyrosine kinase syk is associated with and activated by the il-2 receptor: Possible link with the c-myc induction pathway

Abstract

The IL-2 receptor (IL-2R) consists of three subunits, the IL-2R alpha, IL-2R beta, and IL-2R gamma chains. The IL-2-induced proliferative signals emanate from the cytoplasmic domains of IL-2R beta and IL-2R gamma, but the nature and function of the signaling molecules that transmit these signals are not fully understood. Here, we report that Syk protein tyrosine kinase (PTK) is physically associated with IL-2R in peripheral blood lymphocytes. cDNA expression studies further revealed that this association is critical for the IL-2-induced activation of Syk PTK, which occurs primarily via the serine-rich region of the IL-2R beta chain, which is essential for proliferative signal transmission. Furthermore, we provide evidence that in the hematopoietic cell line, BAF-B03, the activation of Syk PTK results in the induction of the c-myc gene, an event critical for the cell proliferation. Thus, Syk PTK may be a critical integral member of the signaling molecules engaged by the IL-2R.

IL‐2‐induced gene expression of protein‐tyrosine phosphatase LC‐PTP requires acidic and serine‐rich regions within IL‐2 receptor β chain

“…The membrane proximal, the serine-rich region of IL-2Rfl is essential for activation of JAK-family PTKs [21] and Src-family Syk [22] as well as for c-myc gene induction. On the other hand, the membrane distal, the acidic region of IL-2R,fl is crucial for activation of Src-family PTKs and for c-fos and c-jun gene induction [23].…”

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

“…Activated PI 3-K is most likely then responsible for activation of its downstream kinase Akt (protein kinase B) and p70 S6 kinase (Ahmed et al, 1997;Kuo et al, 1992), which are involved in antiapoptotic and proliferative activities in response to IL-2 (Reif et al, 1997). In addition, the protein tyrosine (Hatakeyama et al, 1991;Minami et al, 1993Minami et al, , 1995Miyazaki et al, 1998;Figure 2). However, the biological signi®cance of their activation in vivo is not yet clear and requires further investigation.…”

Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors

“…The c-myc gene is induced in response to the proliferative signals elicited by extracellular stimuli, including IL-6. The non-receptor tyrosine kinases c-src (Barone and Courtneidge, 1995), syk (Minami et al, 1995), and Jak (Kawahara et al, 1995;Sakamaki et al, 1992;Watanabe et al, 1996), and the oncogenes, v-src, v-abl, bcr-abl, and v-akt all induce c-myc mRNA expression (Cleveland et al, 1989;Kuchino et al, 1985;Sovova et al, 1993;Stewart et al, 1995). Kiuchi et al (1999) showed that STAT3 mediates the induction of the c-myc gene upon gp130 stimulation.…”