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J. Cell Biol. 147 (4): 707-714

Copyright © 1999 by the Rockefeller University Press.

Original Article

Protein Tyrosine Phosphatase {alpha} (Ptp{alpha}) and Contactin Form a Novel Neuronal Receptor Complex Linked to the Intracellular Tyrosine Kinase Fyn

Li Zenga, Luca D'Alessandrib, Markus B. Kalouseka, Lloyd Vaughanb, , and Catherine J. Pallena

a Institute for Molecular and Cell Biology, Singapore 117609, Republic of Singapore
b Institute for Biochemistry, ETH-Zurich, CH-8092 Zurich, Switzerland
Institute for Molecular and Cell Biology, 30 Medical Drive, Singapore 117609, Republic of Singapore.65-779-111765-874-3742

Abstract: Glycosyl phosphatidylinositol (GPI)–linked receptors and receptor protein tyrosine phosphatases (RPTPs), both play key roles in nervous system development, although the molecular mechanisms are largely unknown. Despite lacking a transmembrane domain, GPI receptors can recruit intracellular src family tyrosine kinases to receptor complexes. Few ligands for the extracellular regions of RPTPs are known, relegating most to the status of orphan receptors. We demonstrate that PTP{alpha}, an RPTP that dephosphorylates and activates src family kinases, forms a novel membrane-spanning complex with the neuronal GPI-anchored receptor contactin. PTP{alpha} and contactin associate in a lateral (cis) complex mediated through the extracellular region of PTP{alpha}. This complex is stable to isolation from brain lysates or transfected cells through immunoprecipitation and to antibody-induced coclustering of PTP{alpha} and contactin within cells. This is the first demonstration of a receptor PTP in a cis configuration with another cell surface receptor, suggesting an additional mode for regulation of a PTP. The transmembrane and catalytic nature of PTP{alpha} indicate that it likely forms the transducing element of the complex, and we postulate that the role of contactin is to assemble a phosphorylation-competent system at the cell surface, conferring a dynamic signal transduction capability to the recognition element.

Key Words: PTP{alpha} • tyrosine phosphatase • glycosyl phosphatidylinositol • neural signal transduction

L. Zeng, L. D'Alessandri, and M.B. Kalousek contributed equally to this work.

M.B. Kalousek's present address is Laves-Arzneimittel GmbH, CH-6247 Schötz, Switzerland.

Abbreviations used in this paper: FN-III, fibronectin type III; GPI, glycosyl phosphatidylinositol; PTP, protein tyrosine phosphatase; RPTP, receptor protein tyrosine phosphatase; VSVG, vaccinia stomatitis virus glycoprotein.

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