Tec kinase associates with c-kit and is tyrosine phosphorylated and activated following stem cell factor binding.

Abstract

Stem cell factor (SCF) plays a crucial role in hematopoiesis through its interaction with the receptor tyrosine kinase c-kit. However, the signaling events that are activated by this interaction and involved in the control of growth or differentiation are not completely understood. We demonstrate here that Tec, a cytoplasmic, src-related kinase, physically associates with c-kit through a region that contains a proline-rich motif, amino terminal of the SH3 domain. Following SCF binding, Tec is tyrosine phosphorylated and its in vitro kinase activity is increased. Tyrosine phosphorylation of Tec is not detected in the response to other cytokines controlling hematopoiesis, including colony-stimulating factor-1 (CSF-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-3 (IL-3). Conversely, the cytoplasmic kinase JAK2 is activated by IL-3 but not by SCF stimulation. The activation of distinct cytoplasmic kinases may account for the synergy seen in the actions of SCF and IL-3 on hematopoietic stem cells.

Isoforms of c-KIT differ in activation of signalling pathways and transformation of NIH3T3 fibroblasts

“…The data presented here imply major di erences between the isoforms in their interaction with signal transducing molecules. It will be important to investigate their interactions with phosphatases such as SHP-1 which is associated with c- KIT (Yi and Ihle, 1993) and a range of proteins such as Shc (Matsuguchi et al, 1994), Tec (Tang et al, 1994), Lyn , PLCg1 (Rottapel et al, 1991;Herbst et al, 1995b), p120 CBL (Wisniewski et al, 1996), JAK2 (Weiler et al, 1996) and Stat 1 that are known to be recruited or activated on SLF binding to c-KIT.…”

Tec is involved in G protein-coupled receptor- and integrin-mediated signalings in human blood platelets

“…Tec is a non-receptor type tyrosine kinase which has been reported to be phosphorylated on tyrosine residues upon cytokine stimulation of hematopoietic cells (Tang et al, 1994;Machide et al, 1995;Mano et al, 1995;Matsuda et al, 1995;Miyazato et al, 1996;Yamashita et al, 1996). Based on the previous ®ndings that Tec is tyrosine phosphorylated in response to thrombopoietin (TPO) in a TPO-dependent cell line and that TPO induces tyrosine phosphorylation in multiple platelet proteins (Kojima et al, 1995), we ®rst assayed whether Tec is tyrosine phosphorylated in response to TPO.…”

“…Furthermore, secondary agonists such as ADP and thromboxane A 2 were not required for thrombin-induced tyrosine phosphorylation in Tec. So far, Tec has been reported to be tyrosine phosphorylated by stimulation with cytokines such as SCF (Tang et al, 1994), G-CSF , IL-6 (Matsuda et al, 1995), EPO (Machide et al, 1995), IL-3 and TPO in nucleated cells. We here demonstrate for the ®rst time that Tec is also tyrosine phosphorylated in the downstream signaling pathways of the activation of G protein-coupled receptors.…”

“…Although its exact role in cell growth and di erentiation has not been elucidated, Tec kinase becomes phosphorylated in tyrosine residues and activated upon stimulation with various cytokines such as stem cell factor (SCF) (Tang et al, 1994), granulocyte colony-stimulating factor (G-CSF) , interleukin-6 (IL-6) (Matsuda et al, 1995), erythropoietin (EPO) (Machide et al, 1995), interleukin-3 (IL-3) , and thrombopoietin (TPO) . Upon cytokine stimulation, Tec associates with gp 130, a signal transducer of the IL-6 family (Matsuda et al, 1995), and c-kit (Tang et al, 1994).…”

“…Upon cytokine stimulation, Tec associates with gp 130, a signal transducer of the IL-6 family (Matsuda et al, 1995), and c-kit (Tang et al, 1994). Furthermore, it has been revealed that Tec links cytokine receptors to phosphatidylinositol 3-kinase through JAKs (Janus kinases) (Takahashi-Tezuka et al, 1997).…”