Regulation of receptor tyrosine kinase signaling by protein tyrosine phosphatase-1B

Fawaz Haj, Boyka Markova, Lori D. Klaman, Frank D. Bohmer, Benjamin G. Neel

Research output: Contribution to journalArticle

201 Citations (Scopus)

Abstract

Receptor tyrosine kinases (RTKs) are key regulators of cellular homeostasis. Based on in vitro and ex vivo studies, protein tyrosine phosphatase-1B (PTP1B) was implicated in the regulation of several RTKs, yet mice lacking PTP1B show defects mainly in insulin and leptin receptor signaling. To address this apparent paradox, we studied RTK signaling in primary and immortalized fibroblasts from PTP1B-/- mice. After growth factor treatment, cells lacking PTP1B exhibit increased and sustained phosphorylation of the epidermal growth factor receptor (EGFR) and the platelet-derived growth factor receptor (PDGFR). However, Erk activation is enhanced only slightly, and there is no increase in Akt activation in PTP1B-deficient cells. Our results show that PTP1B does play a role in regulating EGFR and PDGFR phosphorylation but that other signaling mechanisms can largely compensate for PTP1B deficiency. In-gel phosphatase experiments suggest that other PTPs may help to regulate the EGFR and PDGFR in PTP1B-/- fibroblasts. This and other compensatory mechanisms prevent widespread, uncontrolled activation of RTKs in the absence of PTP1B and probably explain the relatively mild effects of PTP1B deletion in mice.

Original languageEnglish (US)
Pages (from-to)739-744
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number2
DOIs
StatePublished - Jan 10 2003
Externally publishedYes

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Non-Receptor Type 1 Protein Tyrosine Phosphatase
Receptor Protein-Tyrosine Kinases
Platelet-Derived Growth Factor Receptors
Epidermal Growth Factor Receptor
Phosphorylation
Chemical activation
Fibroblasts
Leptin Receptors
Insulin Receptor
Phosphoric Monoester Hydrolases
Intercellular Signaling Peptides and Proteins
Homeostasis
Gels

ASJC Scopus subject areas

  • Biochemistry

Cite this

Regulation of receptor tyrosine kinase signaling by protein tyrosine phosphatase-1B. / Haj, Fawaz; Markova, Boyka; Klaman, Lori D.; Bohmer, Frank D.; Neel, Benjamin G.

In: Journal of Biological Chemistry, Vol. 278, No. 2, 10.01.2003, p. 739-744.

Research output: Contribution to journalArticle

Haj, Fawaz ; Markova, Boyka ; Klaman, Lori D. ; Bohmer, Frank D. ; Neel, Benjamin G. / Regulation of receptor tyrosine kinase signaling by protein tyrosine phosphatase-1B. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 2. pp. 739-744.
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