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Science 17 July 1998:
Vol. 281. no. 5375, pp. 413 - 416
DOI: 10.1126/science.281.5375.413
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Reports

Uncoupling of Nonreceptor Tyrosine Kinases from PLC-gamma 1 in an SLP-76-Deficient T Cell

Deborah Yablonski, Michelle R. Kuhne, Theresa Kadlecek, Arthur Weiss *

Activation of nonreceptor protein tyrosine kinases (PTKs) is essential for T cell receptor (TCR) responsiveness; however, the function of individual PTK substrates is often uncertain. A mutant T cell line was isolated that lacked expression of SLP-76 (SH2 domain-containing leukocyte protein of 76 kilodaltons), a hematopoietically expressed adaptor protein and PTK substrate. SLP-76 was not required for TCR-induced tyrosine phosphorylation of most proteins, but was required for optimal tyrosine phosphorylation and activation of phospholipase C-gamma 1 (PLC-gamma 1), as well as Ras pathway activation. TCR-inducible gene expression was dependent on SLP-76. Thus, coupling of TCR-regulated PTKs to downstream signaling pathways requires SLP-76.

Departments of Medicine and of Microbiology and Immunology and the Howard Hughes Medical Institute, Box , University of California, San Francisco, San Francisco, CA 94143-0795, USA.
*   To whom correspondence should be addressed. E-mail: aweiss{at}itsa.ucsf.edu

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   Abstract »    Full Text »    PDF »
TCR/CD3-Induced Activation and Binding of Emt/Itk to Linker of Activated T Cell Complexes: Requirement for the Src Homology 2 Domain.
K. A. Ching, J. A. Grasis, P. Tailor, Y. Kawakami, T. Kawakami, and C. D. Tsoukas (2000)
J. Immunol. 165, 256-262
   Abstract »    Full Text »    PDF »
In vitro and in vivo macrophage function can occur independently of SLP-76.
P. S. Myung, J. L. Clements, D. W. White, Z. A. Malik, J. S. Cowdery, L.-A. H. Allen, J. T. Harty, D. J. Kusner, and G. A. Koretzky (2000)
Int. Immunol. 12, 887-897
   Abstract »    Full Text »    PDF »
GRID: A Novel Grb-2-Related Adapter Protein That Interacts with the Activated T Cell Costimulatory Receptor CD28.
J. H. Ellis, C. Ashman, M. N. Burden, K. E. Kilpatrick, M. A. Morse, and P. A. Hamblin (2000)
J. Immunol. 164, 5805-5814
   Abstract »    Full Text »    PDF »
Cloning and Characterization of Human Lnk, an Adaptor Protein with Pleckstrin Homology and Src Homology 2 Domains that Can Inhibit T Cell Activation.
Y. Li, X. He, J. Schembri-King, S. Jakes, and J. Hayashi (2000)
J. Immunol. 164, 5199-5206
   Abstract »    Full Text »    PDF »
RasGRP links T-cell receptor signaling to Ras.
J. O. Ebinu, S. L. Stang, C. Teixeira, D. A. Bottorff, J. Hooton, P. M. Blumberg, M. Barry, R. C. Bleakley, H. L. Ostergaard, and J. C. Stone (2000)
Blood 95, 3199-3203
   Abstract »    Full Text »    PDF »
Dok-3, a Novel Adapter Molecule Involved in the Negative Regulation of Immunoreceptor Signaling.
S. Lemay, D. Davidson, S. Latour, and A. Veillette (2000)
Mol. Cell. Biol. 20, 2743-2754
   Abstract »    Full Text »
A BASH/SLP-76-related adaptor protein MIST/Clnk involved in IgE receptor-mediated mast cell degranulation.
R. Goitsuka, H. Kanazashi, H. Sasanuma, Y.-i. Fujimura, Y. Hidaka, A. Tatsuno, C. Ra, K. Hayashi, and D. Kitamura (2000)
Int. Immunol. 12, 573-580
   Abstract »    Full Text »    PDF »
Vav Synergizes with Protein Kinase C{Theta} to Mediate IL-4 Gene Expression in Response to CD28 Costimulation in T Cells.
S. P. Hehner, M. Li-Weber, M. Giaisi, W. Droge, P. H. Krammer, and M. L. Schmitz (2000)
J. Immunol. 164, 3829-3836
   Abstract »    Full Text »    PDF »
A Population of In Vivo Anergized T Cells with a Lower Activation Threshold for the Induction of CD25 Exhibit Differential Requirements in Mobilization of Intracellular Calcium and Mitogen-Activated Protein Kinase Activation.
O. Utting, S.-J. Teh, and H.-S. Teh (2000)
J. Immunol. 164, 2881-2889
   Abstract »    Full Text »    PDF »
Regulatory and Signaling Properties of the Vav Family.
X. R. Bustelo (2000)
Mol. Cell. Biol. 20, 1461-1477
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B cell development and activation defects resulting in xid-like immunodeficiency in BLNK/SLP-65-deficient mice.
S. Xu, J. E.-L. Tan, E. P.-Y. Wong, A. Manickam, S. Ponniah, and K.-P. Lam (2000)
Int. Immunol. 12, 397-404
   Abstract »    Full Text »    PDF »
MEK Activity Regulates Negative Selection of Immature CD4+CD8+ Thymocytes.
U. Bommhardt, Y. Scheuring, C. Bickel, R. Zamoyska, and T. Hunig (2000)
J. Immunol. 164, 2326-2337
   Abstract »    Full Text »    PDF »
Functional Association between SLAP-130 and SLP-76 in Jurkat T Cells.
N. J. Boerth, B. A. Judd, and G. A. Koretzky (2000)
J. Biol. Chem. 275, 5143-5152
   Abstract »    Full Text »    PDF »
Differential T-Cell Antigen Receptor Signaling Mediated by the Src Family Kinases Lck and Fyn.
M. F. Denny, B. Patai, and D. B. Straus (2000)
Mol. Cell. Biol. 20, 1426-1435
   Abstract »    Full Text »
Src-like Adaptor Protein (SLAP) Is a Negative Regulator of T Cell Receptor Signaling.
T. Sosinowski, A. Pandey, V. M. Dixit, and A. Weiss (2000)
J. Exp. Med. 191, 463-474
   Abstract »    Full Text »    PDF »
An Ultra-High Throughput Screening Approach for an Adenine Transferase Using Fluorescence Polarization.
Z. Li, S. Mehdi, I. Patel, J. Kawooya, M. Judkins, W. Zhang, K. Diener, A. Lozada, and D. Dunnington (2000)
J Biomol Screen 5, 31-37
   Abstract »    PDF »


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