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Molecular and cellular biology
Apr, 2013;33 (7): 1430-41.

Receptor protein tyrosine phosphatase-receptor tyrosine kinase substrate screen identifies EphA2 as a target for LAR in cell migration.

Hojin Lee, Anton M Bennett
Author Information
  1. Hojin Lee: Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, USA.
PMID: 23358419 DOI: 10.1128/MCB.01708-12

Abstract

Receptor tyrosine kinases (RTKs) exist in equilibrium between tyrosyl-phosphorylated and dephosphorylated states. Despite a detailed understanding of how RTKs become tyrosyl phosphorylated, much less is known about RTK tyrosyl dephosphorylation. Receptor protein tyrosine phosphatases (RPTPs) can play essential roles in the dephosphorylation of RTKs. However, a complete understanding of the involvement of the RPTP subfamily in RTK tyrosyl dephosphorylation has not been established. In this study, we have employed a small interfering RNA (siRNA) screen to identify RPTPs in the human genome that serve as RTK phosphatases. We observed that each RPTP induced a unique fingerprint of tyrosyl phosphorylation among 42 RTKs. We identified EphA2 as a novel LAR substrate. LAR dephosphorylated EphA2 at phosphotyrosyl 930, uncoupling Nck1 from EphA2 and thereby attenuating EphA2-mediated cell migration. These results demonstrate that each RPTP exerts a unique regulatory fingerprint of RTK tyrosyl dephosphorylation and suggest a complex signaling interplay between RTKs and RPTPs. Furthermore, we observed that LAR modulates cell migration through EphA2 site-specific dephosphorylation.

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Grants

  1. P01 DK057751/United States
  2. R01 GM099801/United States

MeSH Term

Adaptor Proteins, Signal Transducing
Animals
COS Cells
Cell Line
Cell Movement
Chlorocebus aethiops
Epithelial Cells
HEK293 Cells
Humans
Oncogene Proteins
Phosphorylation
Protein-Tyrosine Kinases
Receptor, EphA2
Receptor-Like Protein Tyrosine Phosphatases

Chemicals

Adaptor Proteins, Signal Transducing
Nck protein
Oncogene Proteins
Protein-Tyrosine Kinases
Receptor, EphA2
Receptor-Like Protein Tyrosine Phosphatases
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
Article has an altmetric score of 1

Word Cloud

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