Journal of Neuroscience, Vol 13, 4968-4978, Copyright © 1993 by Society for Neuroscience
Protein tyrosine phosphatases expressed in the developing rat brain
M Sahin and S Hockfield
Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510.
Previous studies of the developing nervous system have shown that cell-
cell and cell-matrix interactions are involved in a variety of processes
such as the proliferation, migration, and differentiation of neurons. While
many cell-surface molecules have been identified, the signal transduction
mechanisms through which they modify cellular responses are poorly
understood. Recent studies have described a new and large family of
enzymes, protein tyrosine phosphatases (PTPases), that may play a key role
in transduction of cell surface events. Opposing the actions of protein
tyrosine kinases (PTKs), PTPases can determine the state of tyrosine
phosphorylation of a protein and regulate its function. Within the family
of PTPases, two subgroups have been characterized: low-molecular-weight
cytoplasmic (nonreceptor) PTPases and high-molecular-weight transmembrane
(receptor) PTPases. Many receptor PTPases have fibronectin type III and/or
Ig-like domains in their extracellular domains, suggesting that they have
dual functions: cell adhesion and signal transduction. Such molecules may
play a role in cellular recognition events that mediate the accurate
assembly of the nervous system. Using polymerase chain reaction with
degenerate primers and a neonatal rat cortex cDNA library, we have
identified a number of putative PTPase domains expressed in brain. Three
are characterized here. These three sequences are most abundantly expressed
in the developing cortex and so are named cortex-enriched protein tyrosine
phosphatases (CPTPs) 1, 2, and 3. CPTP1 and CPTP3 show sequence homology to
receptor PTPases and detect multiple high- molecular-weight mRNAs that are
expressed preferentially in the developing CNS. Analysis of a longer cDNA
indicates that CPTP1 and CPTP3 are the first and second phosphatase domains
of a single receptor PTPase. CPTP2 identifies a single, smaller mRNA
species with sequence homology to nonreceptor PTPases. Within the CNS,
mRNAs detected by all three CPTPs are expressed at highest levels during
prenatal and early postnatal days and are downregulated in the adult. In
situ hybridization demonstrates that the CPTPs are expressed by progenitor
cells and developing neurons. The spatial and temporal regulation of CPTPs
suggests that they may play a role in neuronal development.
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