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Selected glimpses into the activation and function of Src kinase

Oncogene volume 19, pages 5620–5635 (2000)Cite this article

Abstract

Since the discovery of the v-src and c-src genes and their products, much progress has been made in the elucidation of the structure, regulation, localization, and function of the Src protein. Src is a non-receptor protein tyrosine kinase that transduces signals that are involved in the control of a variety of cellular processes such as proliferation, differentiation, motility, and adhesion. Src is normally maintained in an inactive state, but can be activated transiently during cellular events such as mitosis, or constitutively by abnormal events such as mutation (i.e. v-Src and some human cancers). Activation of Src occurs as a result of disruption of the negative regulatory processes that normally suppress Src activity, and understanding the various mechanisms behind Src activation has been a target of intense study. Src associates with cellular membranes, in particular the plasma membrane, and endosomal membranes. Studies indicate that the different subcellular localizations of Src could be important for the regulation of specific cellular processes such as mitogenesis, cytoskeletal organization, and/or membrane trafficking. This review will discuss the history behind the discovery and initial characterization of Src and the regulatory mechanisms of Src activation, in particular, regulation by modification of the carboxy-terminal regulatory tyrosine by phosphatases and kinases. Its focus will then turn to the different subcellular localizations of Src and the possible roles of nuclear and perinuclear targets of Src. Finally, a brief section will review some of our present knowledge regarding Src involvement in human cancers.

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Acknowledgements

We thank the members of our laboratory and S Robbins for their comments and suggestions regarding the manuscript. Experimental work in our laboratory was supported by grants from the Medical Research Council of Canada, the National Cancer Institute of Canada, the Canadian Breast Cancer Research Initiative, and the Alberta Breast Cancer Foundation. A Jakymiw is the recipient of an MRC predoctoral studentship, DJ Fujita is a Scientist of the Alberta Heritage Foundation for Medical Research.

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  1. Department of Biochemistry and Molecular Biology, Cancer Biology Research Group, University of Calgary Medical Center, 3330 Hospital Dr. N.W., Calgary, Alberta, T2N 4N1, Canada

    Jeffrey D Bjorge, Andrew Jakymiw & Donald J Fujita

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  1. Jeffrey D Bjorge
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Bjorge, J., Jakymiw, A. & Fujita, D. Selected glimpses into the activation and function of Src kinase. Oncogene 19, 5620–5635 (2000). https://doi.org/10.1038/sj.onc.1203923

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