¹The Department of Medicine, Division of Dermatology and the Norris Cancer Center, the University of Southern California Keck School of Medicine, 1303 North Mission Road, Los Angeles, California CA 90033, USA

²The Greater Los Angeles Veteran Administration Healthcare System, Los Angeles, California, USA

Correspondence to: W Li, The Department of Medicine, Division of Dermatology and the Norris Cancer Center, the University of Southern California Keck School of Medicine, 1303 North Mission Road, Los Angeles, California CA 90033, USA. E-mail: wli@hsc.usc.edu

In response to extracellular signals, cell surface receptors engage in connections with multiple intracellular signaling pathways, leading to the cellular responses such as survival, migration, proliferation and differentiation. The 'pYSH2/SH3effector' connection is a frequently used scheme by many cell surface receptors, in which SH2/SH3-containing adapters connect protein tyrosine phosphorylation to a variety of downstream effector pathways. Following the initial landmark finding that Grb2 adapter links the receptors to the Ras pathway leading to DNA synthesis, recent studies have revealed that the biological function of the SH2/SH3 adapter Nck/Dock is to link cell surface receptors to the actin cytoskeleton. For example, in the evolutionarily-conserved signaling network, GEF-Rac-Nck-Pak, Nck 'fixes up' the interaction of Pak with its upstream activator, Rac. The activated Pak then regulates the cytoskeletal dynamics. The fact that the majority of the more than 20 Nck-SH3-associated effectors are regulators of the actin cytoskeleton suggests that Nck/Dock regulates, via binding to distinct effectors, various cell type-specific motogenic responses. This review focuses on our current understanding of Nck/Dock function. Due to the number and complexity of the terminologies used in this review, a 'Glossary of Terms' is provided to help reduce confusions. Oncogene (2001) 20, 6403-6417.

Src-homology domains; adapters; tyrosine kinases; signal transduction; cytoskeleton