The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/11/1527/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 10, November 15, 1999 1527-1534


Original Article

Clnk, a Novel Slp-76–Related Adaptor Molecule Expressed in Cytokine-Stimulated Hemopoietic Cells

Ming Yu Caoa, Dominique Davidsona, Jie Yua, Sylvain Latoura, and André Veillettea,b,c,d

a McGill Cancer Centre, McGill University, Montréal, Québec, Canada H3G 1Y6
b Department of Biochemistry, McGill University, Montréal, Québec, Canada H3G 1Y6
c Department of Oncology, McGill University, Montréal, Québec, Canada H3G 1Y6
d Department of Medicine, McGill University, Montréal, Québec, Canada H3G 1Y6
McGill Cancer Centre, Rm. 715, McIntyre Medical Sciences Bldg., McGill University, 3655 Drummond St., Montréal, Québec, Canada H3G 1Y6.514-398-4438514-398-8936

andrev{at}med.mcgill.ca

We have identified a novel Src homology 2 domain–containing leukocyte protein of 76 kD (SLP-76)–related molecule which we have termed Clnk (for cytokine-dependent hemopoietic cell linker). Unlike its relatives SLP-76 and B cell linker protein (Blnk), Clnk is not expressed uniformly within a given hemopoietic cell lineage. Even though it can be detected in several cell types, including T cells, natural killer cells, and mast cells, its expression seems to be strictly dependent on sustained exposure to cytokines such as interleukin (IL)-2 and IL-3. Strong support for the notion that Clnk is involved in immunoreceptor signaling was provided by the observation that it inducibly associated with at least one tyrosine-phosphorylated polypeptide (p92) in response to immunoreceptor stimulation. Moreover, transient expression of Clnk caused an increase in immunoreceptor-mediated signaling events in a T cell line. Taken together, these results show that Clnk is a novel member of the SLP-76 family selectively expressed in cytokine-stimulated hemopoietic cells. Furthermore, they suggest that Clnk may be involved in a cross-talk mechanism between cytokine receptor and immunoreceptor signaling.

Key Words: adaptor • SLP-76 • Blnk • signaling • lymphocytes


1used in this paper: BCR, B cell antigen receptor; Blnk, B cell linker protein; BMMC, bone marrow–derived mast cell; Clnk, cytokine-dependent hemopoietic cell linker; Gads, Grb2-related adaptor downstream of Shc; NFAT, nuclear factor of activated T cells; PECAM, platelet-endothelial cell adhesion molecule; PLC, phospholipase C; RAH, rabbit anti–hamster; SAM, sheep anti–mouse; SH2, Src homology 2; SLP, SH2 domain–containing leukocyte protein of 76 kD

M.Y. Cao and D. Davidson contributed work of equal importance to this paper and both should be viewed as first author.

© 1999 The Rockefeller University Press


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