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J Biol Chem, Vol. 273, Issue 39, 25171-25178, September 25, 1998

Identification of Nck Family Genes, Chromosomal Localization, Expression, and Signaling Specificity

Min ChenDagger , Hongyun She, Elizabeth M. Davisparallel , Catherine M. Spicer**, Leopold Kim, Ruibao Ren**, Michelle M. Le Beauparallel , and Wei Li

From the  Ben May Institute for Cancer Research and the Department of Pharmacological and Physiological Sciences, the Dagger  Department of Biochemistry and Molecular Biology, and the parallel  Section of Hematology and Oncology, the Department of Medicine, the University of Chicago, Chicago, Illinois 60637 and the ** Rosenstiel Basic Medical Sciences Research Center and Department of Biology, Brandeis University, Waltham, Massachusetts 02254

Already a dozen molecules share binding to the Src homology (SH) 3 domains of human Nck, an SH3-SH3-SH3-SH2 adapter protein. We reason that there may be multiple gene members of Nck to accommodate the large binding repertoires. Here we report identification of novel human and mouse Nck genes and rename them as the Nckalpha and Nckbeta genes (including the human Nckalpha , human Nckbeta , mouse Nckalpha , and mouse Nckbeta genes). Nckalpha and Nckbeta share 68% amino acid identity, whereas the two Nckalpha and two Nckbeta across the species show 96% identity to each other. The human Nckbeta gene is mapped to 2q12, whereas the human Nckalpha gene has previously been mapped at 3q21. Antibodies specifically against Nckalpha and Nckbeta detect Nckalpha and Nckbeta with an identical molecular mass in the same cells of various origins. Ectopically expressed Nckbeta , but not its SH2 domain mutant, strongly inhibits epidermal growth factor- and platelet-derived growth factor-stimulated DNA synthesis. Consistently, epidermal growth factor receptor and platelet-derived growth factor receptor preferentially interact with Nckbeta over Nckalpha in vitro. This study indicates that Nck is a multiple gene family and that each gene may have its own signaling specificity. Because previous anti-Nck (human Nckalpha ) antibodies cross-react with Nckbeta , reassessment of those studies with specific Nck genes would be necessary.

Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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