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Cell Signal. 2005 Jan;17(1):103-9.

Lyn contributes to regulation of multiple Kit-dependent signaling pathways in murine bone marrow mast cells.

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  • 1Basic Research Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, Building 567, Room 226, Frederick MD 21702, USA.


SCF induces autophosphorylation of Kit and activates a variety of signaling components including Jnks, Erks, PI 3 Kinase, the JAK-Stat pathway and members of the Src family. Previously we showed that Lyn is activated at multiple points during SCF-induced cell cycle progression and contributes to SCF-mediated growth, chemotaxis and internalization of Kit. However, the Kit-dependent biochemical events that require Lyn are unknown. In this study, we used Lyn-deficient bone marrow mast cells (BMMC) to examine the contribution of this Src family member to tyrosine phosphorylation of Kit and SCF-induced activation of Jnks, Akt, Stat3 and Erks. Although surface expression of Kit was increased in Lyn-deficient BMMC, SCF-induced phosphorylation and growth was reduced compared to wild-type BMMC. Downstream of Kit, SCF-induced activation of Jnks was markedly reduced in Lyn-deficient BMMC. Further, Lyn was required for SCF-induced tyrosine phosphorylation of Stat3. Interestingly, Kit was constitutively associated with PI 3 Kinase in Lyn-deficient BMMC and this correlated with constitutive phosphorylation of Akt. This was in marked contrast to wild-type BMMC, where both these events were induced by SCF. These data indicate that in BMMC, Lyn contributes to SCF-induced phosphorylation of Kit, as well as phosphorylation of Jnks and Stat3. In contrast, Lyn may negatively regulate the PI 3 Kinase/Akt pathway. The opposing effects of Lyn on these signaling pathways may explain the pleiotropic effects ascribed to this Src family member in the literature.

Copyright 2004 Elsevier Inc.

[PubMed - indexed for MEDLINE]
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