Protein tyrosine phosphatases in neuronal development

Date of Award




Degree Name

Doctor of Philosophy (Ph.D.)


Molecular and Cellular Pharmacology

First Committee Member

John L. Bixby - Committee Chair


The control of neural development and, in particular, of axon growth, involves the regulation of tyrosine phosphorylation. Until now, our understanding of the importance of tyrosine phosphorylation in growth and development has come predominantly from studies on tyrosine kinases. Emerging evidence suggests that protein tyrosine phosphatases, the enzymatic counterpoint to tyrosine kinases, may serve an important role in regulating tyrosine phosphorylation and potentially neuronal development and function. As yet, the full repertoire of protein tyrosine phosphatases (PTPs) expressed in the developing nervous system is unknown. We have used an RT/PCR-based approach for the identification of PTPs expressed in the chick brain during the time of neuronal differentiation. With this approach, we have identified two novel RPTPs; one of these, designated CRYP-2, is a CAM-related RPTP selectively expressed in the embryonic nervous system. Full-length cloning of CRYP-2 reveals that it is a receptor-type PTP with an adhesion molecule-like extracellular region comprising fibronectin type III repeats and a single catalytic domain in the intracellular region. It is alternatively spliced in the juxtamembrane region, similar to other PTPs recently cloned. CRYP-2 mRNA is strongly expressed in brain during the time of axon growth; it is downregulated towards the end of embryogenesis. Western blot analysis identifies a 330 kDa glycoprotein as CRYP-2, and confirms that the protein is down regulated after hatching. Immunostaining of cerebellar neurons in vitro reveals that CRYP-2 is expressed on neurons, but not glia, and is present on cell bodies and processes. The CAM-like structure, developmental pattern of expression, and neuronal-specific localization of the CRYP-2 PTP suggest that it is involved in neuronal differentiation, particularly axon growth.


Biology, Molecular; Biology, Neuroscience

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