Tyrosine phosphorylation of Pyk2 is selectively regulated by Fyn during TCR signaling

Dapeng Qian, Sima Lev, Nicolai S C Van Oers, Ivan Dikic, Joseph Schlessinger, Arthur Weiss

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

The Src family protein tyrosine kinases (PTKs), Lck and Fyn, are coexpressed in T cells and perform crucial functions involved in the initiation of T cell antigen receptor (TCR) signal transduction. However, the mechanisms by which Lck and Fyn regulate TCR signaling are still not completely understood. One important question is whether Lck and Fyn have specific targets or only provide functional redundancy during TCR signaling. We have previously shown that Lck plays a major role in the tyrosine phosphorylation of the TCR-ζ chain and the ZAP-70 PTK. In an effort to identify the targets that are specifically regulated by Fyn, we have studied the tyrosine phosphorylation of Pyk2, a recently discovered new member of the focal adhesion kinase family PTK. We demonstrated that Pyk2 was rapidly tyrosine phosphorylated following TCR stimulation. TCR-induced tyrosine phosphorylation of Pyk2 was selectively dependent on Fyn but not Lck. Moreover, in heterologous COS-7 cells, coexpression of Pyk2 with Fyn but not Lck resulted in substantial increases in Pyk2 tyrosine phosphorylation. The selective regulation of Pyk2 tyrosine phosphorylation by Fyn in vivo correlated with the preferential phosphorylation of Pyk2 by Fyn in vitro. Our results demonstrate that Pyk2 is a specific target regulated by Fyn during TCR signaling.

Original languageEnglish (US)
Pages (from-to)1253-1259
Number of pages7
JournalJournal of Experimental Medicine
Volume185
Issue number7
DOIs
StatePublished - Apr 7 1997

Fingerprint

T-Cell Antigen Receptor
Tyrosine
Phosphorylation
src-Family Kinases
ZAP-70 Protein-Tyrosine Kinase
Focal Adhesion Protein-Tyrosine Kinases
COS Cells
Protein-Tyrosine Kinases
Signal Transduction
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Tyrosine phosphorylation of Pyk2 is selectively regulated by Fyn during TCR signaling. / Qian, Dapeng; Lev, Sima; Van Oers, Nicolai S C; Dikic, Ivan; Schlessinger, Joseph; Weiss, Arthur.

In: Journal of Experimental Medicine, Vol. 185, No. 7, 07.04.1997, p. 1253-1259.

Research output: Contribution to journalArticle

Qian, Dapeng ; Lev, Sima ; Van Oers, Nicolai S C ; Dikic, Ivan ; Schlessinger, Joseph ; Weiss, Arthur. / Tyrosine phosphorylation of Pyk2 is selectively regulated by Fyn during TCR signaling. In: Journal of Experimental Medicine. 1997 ; Vol. 185, No. 7. pp. 1253-1259.
@article{1917df89ad4d470aa07475262fea059d,
title = "Tyrosine phosphorylation of Pyk2 is selectively regulated by Fyn during TCR signaling",
abstract = "The Src family protein tyrosine kinases (PTKs), Lck and Fyn, are coexpressed in T cells and perform crucial functions involved in the initiation of T cell antigen receptor (TCR) signal transduction. However, the mechanisms by which Lck and Fyn regulate TCR signaling are still not completely understood. One important question is whether Lck and Fyn have specific targets or only provide functional redundancy during TCR signaling. We have previously shown that Lck plays a major role in the tyrosine phosphorylation of the TCR-ζ chain and the ZAP-70 PTK. In an effort to identify the targets that are specifically regulated by Fyn, we have studied the tyrosine phosphorylation of Pyk2, a recently discovered new member of the focal adhesion kinase family PTK. We demonstrated that Pyk2 was rapidly tyrosine phosphorylated following TCR stimulation. TCR-induced tyrosine phosphorylation of Pyk2 was selectively dependent on Fyn but not Lck. Moreover, in heterologous COS-7 cells, coexpression of Pyk2 with Fyn but not Lck resulted in substantial increases in Pyk2 tyrosine phosphorylation. The selective regulation of Pyk2 tyrosine phosphorylation by Fyn in vivo correlated with the preferential phosphorylation of Pyk2 by Fyn in vitro. Our results demonstrate that Pyk2 is a specific target regulated by Fyn during TCR signaling.",
author = "Dapeng Qian and Sima Lev and {Van Oers}, {Nicolai S C} and Ivan Dikic and Joseph Schlessinger and Arthur Weiss",
year = "1997",
month = "4",
day = "7",
doi = "10.1084/jem.185.7.1253",
language = "English (US)",
volume = "185",
pages = "1253--1259",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "7",

}

TY - JOUR

T1 - Tyrosine phosphorylation of Pyk2 is selectively regulated by Fyn during TCR signaling

AU - Qian, Dapeng

AU - Lev, Sima

AU - Van Oers, Nicolai S C

AU - Dikic, Ivan

AU - Schlessinger, Joseph

AU - Weiss, Arthur

PY - 1997/4/7

Y1 - 1997/4/7

N2 - The Src family protein tyrosine kinases (PTKs), Lck and Fyn, are coexpressed in T cells and perform crucial functions involved in the initiation of T cell antigen receptor (TCR) signal transduction. However, the mechanisms by which Lck and Fyn regulate TCR signaling are still not completely understood. One important question is whether Lck and Fyn have specific targets or only provide functional redundancy during TCR signaling. We have previously shown that Lck plays a major role in the tyrosine phosphorylation of the TCR-ζ chain and the ZAP-70 PTK. In an effort to identify the targets that are specifically regulated by Fyn, we have studied the tyrosine phosphorylation of Pyk2, a recently discovered new member of the focal adhesion kinase family PTK. We demonstrated that Pyk2 was rapidly tyrosine phosphorylated following TCR stimulation. TCR-induced tyrosine phosphorylation of Pyk2 was selectively dependent on Fyn but not Lck. Moreover, in heterologous COS-7 cells, coexpression of Pyk2 with Fyn but not Lck resulted in substantial increases in Pyk2 tyrosine phosphorylation. The selective regulation of Pyk2 tyrosine phosphorylation by Fyn in vivo correlated with the preferential phosphorylation of Pyk2 by Fyn in vitro. Our results demonstrate that Pyk2 is a specific target regulated by Fyn during TCR signaling.

AB - The Src family protein tyrosine kinases (PTKs), Lck and Fyn, are coexpressed in T cells and perform crucial functions involved in the initiation of T cell antigen receptor (TCR) signal transduction. However, the mechanisms by which Lck and Fyn regulate TCR signaling are still not completely understood. One important question is whether Lck and Fyn have specific targets or only provide functional redundancy during TCR signaling. We have previously shown that Lck plays a major role in the tyrosine phosphorylation of the TCR-ζ chain and the ZAP-70 PTK. In an effort to identify the targets that are specifically regulated by Fyn, we have studied the tyrosine phosphorylation of Pyk2, a recently discovered new member of the focal adhesion kinase family PTK. We demonstrated that Pyk2 was rapidly tyrosine phosphorylated following TCR stimulation. TCR-induced tyrosine phosphorylation of Pyk2 was selectively dependent on Fyn but not Lck. Moreover, in heterologous COS-7 cells, coexpression of Pyk2 with Fyn but not Lck resulted in substantial increases in Pyk2 tyrosine phosphorylation. The selective regulation of Pyk2 tyrosine phosphorylation by Fyn in vivo correlated with the preferential phosphorylation of Pyk2 by Fyn in vitro. Our results demonstrate that Pyk2 is a specific target regulated by Fyn during TCR signaling.

UR - http://www.scopus.com/inward/record.url?scp=0030902281&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030902281&partnerID=8YFLogxK

U2 - 10.1084/jem.185.7.1253

DO - 10.1084/jem.185.7.1253

M3 - Article

VL - 185

SP - 1253

EP - 1259

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 7

ER -