| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Receptors and Signal Transduction Section, Oral Infection and Immunity Branch, National Institutes of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892
The protein tyrosine kinase Syk plays an essential role
in Fc
RI-mediated histamine release in mast cells by regulating the
phosphorylation of other proteins. We investigated the functional role
of a putative Syk phosphorylation site, Tyr317. This
tyrosine in the linker region of Syk is a possible site for binding by
the negative regulator Cbl. Syk with Tyr317 mutated to Phe
(Y317F) was expressed in a Syk-negative variant of the RBL-2H3 mast
cells. Compared with cells expressing wild-type Syk, expression of the
Y317F mutant resulted in an increase in the FcRI-mediated tyrosine
phosphorylation of phospholipase C-
and a dramatic enhancement of
histamine release. The in vivo FcRI-induced tyrosine phosphorylation
of wild-type Syk and that of the Y317F mutant were similar. Although
the FcRI-induced tyrosine phosphorylation of total cellular proteins
was enhanced in the cells expressing the Y317F Syk, the phosphorylation
of some other molecules, including the receptor subunits, Vav and
mitogen-activated protein kinase, was not increased. The
FcRI-induced phosphorylation of Cbl was downstream of Syk kinase
activity and was unchanged by expression of the Y317F mutation. These
data indicate that Tyr317 in the linker region of Syk
functions to negatively regulate the signals leading to
degranulation.
This article has been cited by other articles:
|
|
 |
|
  W. Zou, J. L. Reeve, H. Zhao, F. P. Ross, and S. L. Teitelbaum Syk Tyrosine 317 Negatively Regulates Osteoclast Function via the Ubiquitin-Protein Isopeptide Ligase Activity of Cbl J. Biol. Chem., July 10, 2009; 284(28): 18833 - 18839. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yamashita, R. Suzuki, P. S. Backlund, Y. Yamashita, A. L. Yergey, and J. Rivera Differential Dephosphorylation of the FcR{gamma} Immunoreceptor Tyrosine-based Activation Motif Tyrosines with Dissimilar Potential for Activating Syk J. Biol. Chem., October 17, 2008; 283(42): 28584 - 28594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Inubushi, M. Nagano-Fujii, K. Kitayama, M. Tanaka, C. An, H. Yokozaki, H. Yamamura, H. Nuriya, M. Kohara, K. Sada, et al. Hepatitis C virus NS5A protein interacts with and negatively regulates the non-receptor protein tyrosine kinase Syk J. Gen. Virol., May 1, 2008; 89(5): 1231 - 1242. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Lee, Y. M. Kim, N. W. Kim, J. W. Kim, E. Her, B. K. Kim, J. H. Kim, S. H. Ryu, J. W. Park, D. W. Seo, et al. Phospholipase D2 acts as an essential adaptor protein in the activation of Syk in antigen-stimulated mast cells Blood, August 1, 2006; 108(3): 956 - 964. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. Vonakis, S. P. Gibbons Jr, M. J. Rotte, E. A. Brothers, S. C. Kim, K. Chichester, and S. M. MacDonald Regulation of Rat Basophilic Leukemia-2H3 Mast Cell Secretion by a Constitutive Lyn Kinase Interaction with the High Affinity IgE Receptor (Fc{epsilon}RI) J. Immunol., October 1, 2005; 175(7): 4543 - 4554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Qu, S. M. S. Miah, T. Hatani, M. Okazaki, N. Hori-Tamura, H. Yamamura, H. Hotta, and K. Sada Selective Inhibition of Fc{varepsilon}RI-Mediated Mast Cell Activation by a Truncated Variant of Cbl-b Related to the Rat Model of Type 1 Diabetes Mellitus J. Biochem., June 1, 2005; 137(6): 711 - 720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Simon, L. Vanes, R. L. Geahlen, and V. L. J. Tybulewicz Distinct Roles for the Linker Region Tyrosines of Syk in Fc{epsilon}RI Signaling in Primary Mast Cells J. Biol. Chem., February 11, 2005; 280(6): 4510 - 4517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. D. Moon, C. B. Post, D. L. Durden, Q. Zhou, P. De, M. L. Harrison, and R. L. Geahlen Molecular Basis for a Direct Interaction between the Syk Protein-tyrosine Kinase and Phosphoinositide 3-Kinase J. Biol. Chem., January 14, 2005; 280(2): 1543 - 1551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. S. Miah, T. Hatani, X. Qu, H. Yamamura, and K. Sada Point mutations of 3BP2 identified in human-inherited disease cherubism result in the loss of function Genes Cells, November 1, 2004; 9(11): 993 - 1004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhang, Y. J. Chiang, R. J. Hodes, and R. P. Siraganian Inactivation of c-Cbl or Cbl-b Differentially Affects Signaling from the High Affinity IgE Receptor J. Immunol., August 1, 2004; 173(3): 1811 - 1818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Hernandez-Hansen, A. J. Smith, Z. Surviladze, A. Chigaev, T. Mazel, J. Kalesnikoff, C. A. Lowell, G. Krystal, L. A. Sklar, B. S. Wilson, et al. Dysregulated Fc{epsilon}RI Signaling and Altered Fyn and SHIP Activities in Lyn-Deficient Mast Cells J. Immunol., July 1, 2004; 173(1): 100 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Qu, K. Sada, S. Kyo, K. Maeno, S. M. S. Miah, and H. Yamamura Negative regulation of Fc{epsilon}RI-mediated mast cell activation by a ubiquitin-protein ligase Cbl-b Blood, March 1, 2004; 103(5): 1779 - 1786. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. S. Miah, K. Sada, P. T. Tuazon, J. Ling, K. Maeno, S. Kyo, X. Qu, Y. Tohyama, J. A. Traugh, and H. Yamamura Activation of Syk Protein Tyrosine Kinase in Response to Osmotic Stress Requires Interaction with p21-Activated Protein Kinase Pak2/{gamma}-PAK Mol. Cell. Biol., January 1, 2004; 24(1): 71 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhang, E. Berenstein, and R. P. Siraganian Phosphorylation of Tyr342 in the Linker Region of Syk Is Critical for Fc{varepsilon}RI Signaling in Mast Cells Mol. Cell. Biol., December 1, 2002; 22(23): 8144 - 8154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Paolini, R. Molfetta, L. O. Beitz, J. Zhang, A. M. Scharenberg, M. Piccoli, L. Frati, R. Siraganian, and A. Santoni Activation of Syk Tyrosine Kinase Is Required for c-Cbl-mediated Ubiquitination of Fcepsilon RI and Syk in RBL Cells J. Biol. Chem., September 27, 2002; 277(40): 36940 - 36947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sada, S. M. S. Miah, K. Maeno, S. Kyo, X. Qu, and H. Yamamura Regulation of Fcepsilon RI-mediated degranulation by an adaptor protein 3BP2 in rat basophilic leukemia RBL-2H3 cells Blood, August 28, 2002; 100(6): 2138 - 2144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Rao, I. Dodge, and H. Band The Cbl family of ubiquitin ligases: critical negative regulators of tyrosine kinase signaling in the immune system J. Leukoc. Biol., May 1, 2002; 71(5): 753 - 763. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Oda, H. D. Ochs, L. A. Lasky, S. Spencer, K. Ozaki, M. Fujihara, M. Handa, K. Ikebuchi, and H. Ikeda CrkL is an adapter for Wiskott-Aldrich syndrome protein and Syk Blood, May 1, 2001; 97(9): 2633 - 2639. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhang, M. L. Billingsley, R. L. Kincaid, and R. P. Siraganian Phosphorylation of Syk Activation Loop Tyrosines Is Essential for Syk Function. AN IN VIVO STUDY USING A SPECIFIC ANTI-Syk ACTIVATION LOOP PHOSPHOTYROSINE ANTIBODY J. Biol. Chem., November 3, 2000; 275(45): 35442 - 35447. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
