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The Src-like tyrosine kinase Hck is activated by granulocyte colony-stimulating factor (G-CSF) and docks to the activated G-CSF receptor

journal contribution
posted on 1998-10-09, 00:00 authored by Alister WardAlister Ward, J L Monkhouse, X F Csar, I P Touw, P A Bello
Activation of the granulocyte colony-stimulating factor receptor (G-CSF-R) leads to tyrosine-phosphorylation of multiple cytoplasmic components. To date, the kinases Jak1, Jak2, Tyk2, Lyn, and Syk have been implicated in this process. However, it is unknown if other kinases might be involved in the diverse responses from the G-CSF-R, which include mitogenesis, survival, differentiation, and functional activation of responsive cells. The hematopoietic cell kinase (Hck) is a member of the Src-family of kinases known to be expressed in cells of the granulocytic lineage. It also interacts with the gp130 subunit of the LIF/IL-6 receptors, which is closely related to the G-CSF-R, and so represents a good candidate for mediating at least some of the downstream signaling from the G-CSF-R. Therefore, we investigated the activation of Hck by the G-CSF-R in intact cells as well as in vitro. These studies revealed recruitment of Hck to activated G-CSF-R, mediated by direct binding via its SH2 domain to multiple phosphotyrosines of the receptor. In addition, we show that Hck becomes activated upon G-CSF treatment and is, in turn, able to phosphorylate the G-CSF-R, indicating a clear functional and physical involvement in G-CSF signaling.

History

Journal

Biochemical and biophysical research communications

Volume

251

Issue

1

Pagination

117 - 123

Publisher

Elsevier

Location

Amsterdam, The Netherlands

ISSN

0006-291X

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

1998, Academic Press