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Physiological Reviews, Vol. 83, No. 1, January 2003, pp. 1-24; 10.1152/physrev.00016.2002.
Copyright ©2003 by the American Physiological Society
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts
Johnson, Karl G. and
David Van Vactor.
Receptor Protein Tyrosine Phosphatases in Nervous System
Development. Physiol. Rev. 83: 1-24, 2003.
Receptor protein
tyrosine phosphatases (RPTPs) are key regulators of neuronal
morphogenesis in a variety of different vertebrate and invertebrate
systems, yet the mechanisms by which these proteins regulate central
nervous system development are poorly understood. In the past few
years, studies have begun to outline possible models for RPTP function
by demonstrating in vivo roles for RPTPs in axon outgrowth, guidance,
and synaptogenesis. In addition, the crystal structures of several
RPTPs have been solved, numerous downstream effectors of RPTP signaling
have been identified, and a small number of RPTP ligands have been
described. In this review, we focus on how RPTPs transduce signals from
the extracellular environment to the cytoplasm, using a detailed
comparative analysis of the different RPTP subfamilies. Focusing on the
roles RPTPs play in the development of the central nervous system, we
discuss how the elucidation of RPTP crystal structures, the biochemical analysis of phosphatase enzyme catalysis, and the characterization of
complex signal transduction cascades downstream of RPTPs have generated
testable models of RPTP structure and function.
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