scholarly journals ZAP-70 Protein Tyrosine Kinase Is Constitutively Targeted to the T Cell Cortex Independently of its SH2 Domains

1997 ◽  
Vol 137 (7) ◽  
pp. 1639-1649 ◽  
Author(s):  
Russell D.J. Huby ◽  
Makio Iwashima ◽  
Arthur Weiss ◽  
Steven C. Ley
Keyword(s):  
T Cell ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Kinase Domain ◽  
Cell Cortex ◽  
Protein Tyrosine ◽  
Sh2 Domains ◽  
Anchoring Protein ◽  
High Concentrations ◽  
Lck Protein

ZAP-70 is a nonreceptor protein tyrosine kinase that is essential for signaling via the T cell antigen receptor (TCR). ZAP-70 becomes phosphorylated and activated by LCK protein tyrosine kinase after interaction of its two NH2-terminal SH2 domains with tyrosine-phosphorylated subunits of the activated TCR. In this study, the localization of ZAP-70 was investigated by immunofluorescence and confocal microscopy. ZAP-70 was found to be localized to the cell cortex in a diffuse band under the plasma membrane in unstimulated T cells, and this localization was not detectably altered by TCR stimulation. Analysis of mutants indicated that ZAP-70 targeting was independent of its SH2 domains but required its active kinase domain. The specific compartmentalization of ZAP-70 suggests that it may interact with an anchoring protein in the cell cortex via its hinge or kinase domains. It is likely that the maintenance of high concentrations of ZAP-70 at the cell cortex, that only has to move a short distance to interact with phophorylated TCR subunits, facilitates rapid initiation of signaling by the TCR. In addition, as the major increase in tyrosine phosphorylation induced by the TCR also occurs at the cell cortex (Ley, S.C., M. Marsh, C.R. Bebbington, K. Proudfoot, and P. Jordan. 1994. J. Cell. Biol. 125:639–649), ZAP-70 may be localized close to its downstream targets.

Functional dissection of p56lck, a protein tyrosine kinase which mediates interleukin-2-induced activation of the c-fos gene

1994 ◽  
Vol 14 (9) ◽  
pp. 5812-5819
Author(s):  
H Shibuya ◽  
K Kohu ◽  
K Yamada ◽  
E L Barsoumian ◽  
R M Perlmutter ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinases ◽  
Protein Tyrosine Kinase ◽  
Gene Activation ◽  
Interleukin 2 ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Amino Acid Residues ◽  
Protein Tyrosine ◽  
Responsive Element

Members of the newly identified receptor family for cytokines characteristically lack the intrinsic protein tyrosine kinase domain that is a hallmark of other growth factor receptors. Instead, accumulating evidence suggests that these receptors utilize nonreceptor-type protein tyrosine kinases for downstream signal transduction by cytokines. We have shown previously that the interleukin-2 receptor beta-chain interacts both physically and functionally with a Src family member, p56lck, and that p56lck activation leads to induction of the c-fos gene. However, the mechanism linking p56lck activation with c-fos induction remains unelucidated. In the present study, we systematically examined the extent of c-fos promoter activation by expression of a series of p56lck mutants, using a transient cotransfection assay. The results define a set of the essential amino acid residues that regulate p56lck induction of the c-fos promoter. We also provide evidence that the serum-responsive element and sis-inducible element are both targets through which p56lck controls c-fos gene activation.

scholarly journals Insufficient Deactivation of the Protein Tyrosine Kinase Lck Amplifies T-Cell Responsiveness in Acute Coronary Syndrome

2010 ◽  
Vol 106 (4) ◽  
pp. 769-778 ◽  
Author(s):  
Sergey Pryshchep ◽  
Jörg J. Goronzy ◽  
Susmita Parashar ◽  
Cornelia M. Weyand
Keyword(s):  
Acute Coronary Syndrome ◽  
T Cell ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Protein Tyrosine ◽  
Coronary Syndrome

scholarly journals Lymphoid and mesenchymal tumors in transgenic mice expressing the v-fps protein-tyrosine kinase.

1989 ◽  
Vol 9 (12) ◽  
pp. 5491-5499 ◽  
Author(s):  
S P Yee ◽  
D Mock ◽  
P Greer ◽  
V Maltby ◽  
J Rossant ◽  
...  
Keyword(s):  
T Cell ◽  
Transgenic Mice ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Malignant Tumors ◽  
Tumor Formation ◽  
Incomplete Penetrance ◽  
Regulatory Sequences ◽  
Beta Globin ◽  
Protein Tyrosine

src, abl, and fps/fes are prototypes for a family of genes encoding nonreceptor protein-tyrosine kinases. The oncogenic potential of the v-fps protein-tyrosine kinase was investigated by introduction of the gag-fps coding sequence of Fujinami sarcoma virus into the mouse germ line. Transgenic mice with v-fps under the transcriptional control of a 5' human beta-globin promoter (GF) or with both 5' and 3' beta-globin regulatory sequences (GEF) were viable. Unexpectedly, both GF and GEF transgenes were expressed in a wide variety of tissues and induced a spectrum of benign and malignant tumors. These tumors, which included lymphomas, thymomas, fibrosarcomas, angiosarcomas, hemangiomas, and neurofibrosarcomas, developed with various frequencies after latent periods of 2 to 12 months. The majority of lymphoid neoplasms appeared to be of T-cell origin and were monoclonal, as judged by rearrangements of the T-cell receptor beta or immunoglobulin genes. Some tissues that expressed the v-fps oncogene, such as heart, brain, lung, and testes, developed no malignant tumors. The v-fps protein-tyrosine kinase therefore has a broad but not unrestricted range of oncogenic activity in cells of lymphoid and mesenchymal origin. The incomplete penetrance of the neoplastic phenotype and the monoclonality of lymphoid tumors suggest that tumor formation in v-fps mice requires genetic or epigenetic events in addition to expression of the P130gag-fps protein-tyrosine kinase.

scholarly journals Molecular basis for interaction of the protein tyrosine kinase ZAP-70 with the T-cell receptor

Nature ◽  
2007 ◽  
Vol 446 (7137) ◽  
pp. 824-824
Author(s):  
Marcos H. Hatada ◽  
Xiaode Lu ◽  
Ellen R. Laird ◽  
Jeremy Green ◽  
Jay P. Morgenstern ◽  
...  
Keyword(s):  
T Cell ◽  
Tyrosine Kinase ◽  
T Cell Receptor ◽  
Molecular Basis ◽  
Protein Tyrosine Kinase ◽  
Cell Receptor ◽  
Protein Tyrosine

Regulation of T cell receptor signaling by a src family protein-tyrosine kinase (p59fyn)

Cell ◽  
1991 ◽  
Vol 65 (2) ◽  
pp. 281-291 ◽  
Author(s):  
Michael P. Cooke ◽  
Kristin M. Abraham ◽  
Katherine A. Forbush ◽  
Roger M. Perimutter
Keyword(s):  
T Cell ◽  
Tyrosine Kinase ◽  
T Cell Receptor ◽  
Protein Tyrosine Kinase ◽  
Cell Receptor ◽  
Receptor Signaling ◽  
Protein Tyrosine ◽  
Family Protein ◽  
T Cell Receptor Signaling ◽  
Cell Receptor Signaling

scholarly journals The T-cell antigen CD5 acts as a receptor and substrate for the protein-tyrosine kinase p56lck.

1994 ◽  
Vol 14 (5) ◽  
pp. 2862-2870 ◽  
Author(s):  
M Raab ◽  
M Yamamoto ◽  
C E Rudd
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Expression System ◽  
Baculovirus Expression System ◽  
Protein Tyrosine ◽  
Cell Antigen ◽  
Tyrosine Residues ◽  
Baculovirus Expression

CD5 is a T-cell-specific antigen which binds to the B-cell antigen CD72 and acts as a coreceptor in the stimulation of T-cell growth. CD5 associates with the T-cell receptor zeta chain (TcR zeta)/CD3 complex and is rapidly phosphosphorylated on tyrosine residues as a result of TcR zeta/CD3 ligation. However, despite this, the mechanism by which CD5 generates intracellular signals is unclear. In this study, we demonstrate that CD5 is coupled to the protein-tyrosine kinase p56lck and can act as a substrate for p56lck. Coexpression of CD5 with p56lck in the baculovirus expression system resulted in the phosphorylation of CD5 on tyrosine residues. Further, anti-CD5 and anti-p56lck coprecipitated each other in a variety of detergents, including Nonidet P-40 and Triton X-100. Anti-CD5 also precipitated the kinase from various T cells irrespective of the expression of TcR zeta/CD3 or CD4. No binding between p59fyn(T) and CD5 was detected in T cells. The binding of p56lck to CD5 induced a 10- to 15-fold increase in p56lck catalytic activity, as measured by in vitro kinase analysis. In vivo labelling with 32P(i) also showed a four- to fivefold increase in Y-394 occupancy in p56lck when associated with CD5. The use of glutathione S-transferase-Lck fusion proteins in precipitation analysis showed that the SH2 domain of p56lck could recognize CD5 as expressed in the baculovirus expression system. CD5 interaction with p56lck represents a novel variant of a receptor-kinase complex in which receptor can also serve as substrate. The CD5-p56lck interaction is likely to play roles in T-cell signalling and T-B collaboration.

scholarly journals Contributions of F-BAR and SH2 Domains of Fes Protein Tyrosine Kinase for Coupling to the FcεRI Pathway in Mast Cells

2008 ◽  
Vol 29 (2) ◽  
pp. 389-401 ◽  
Author(s):  
Victor A. McPherson ◽  
Stephanie Everingham ◽  
Robert Karisch ◽  
Julie A. Smith ◽  
Christian M. Udell ◽  
...  
Keyword(s):  
Mast Cells ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Regulatory Protein ◽  
Sh2 Domain ◽  
Wild Type ◽  
Protein Tyrosine ◽  
Bar Domain ◽  
Sh2 Domains

ABSTRACT This study investigates the roles of Fer-CIP4 homology (FCH)-Bin/amphiphysin/Rvs (F-BAR) and SH2 domains of Fes protein tyrosine kinase in regulating its activation and signaling downstream of the high-affinity immunoglobulin G (IgE) receptor (FcεRI) in mast cells. Homology modeling of the Fes F-BAR domain revealed conservation of some basic residues implicated in phosphoinositide binding (R113/K114). The Fes F-BAR can bind phosphoinositides and induce tubulation of liposomes in vitro. Mutation of R113/K114 to uncharged residues (RK/QQ) caused a significant reduction in phosphoinositide binding in vitro and a more diffuse cytoplasmic localization in transfected COS-7 cells. RBL-2H3 mast cells expressing full-length Fes carrying the RK/QQ mutation show defects in FcεRI-induced Fes tyrosine phosphorylation and degranulation compared to cells expressing wild-type Fes. This correlated with reduced localization to Lyn kinase-containing membrane fractions for the RK/QQ mutant compared to wild-type Fes in mast cells. The Fes SH2 domain also contributes to Fes signaling in mast cells, via interactions with the phosphorylated FcεRI β chain and the actin regulatory protein HS1. We show that Fes phosphorylates C-terminal tyrosine residues in HS1 implicated in actin stabilization. Thus, coordinated actions of the F-BAR and SH2 domains of Fes allow for coupling to FcεRI signaling and potential regulation the actin reorganization in mast cells.

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