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Science 9 August 1996:
Vol. 273. no. 5276, pp. 792 - 794
DOI: 10.1126/science.273.5276.792
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Reports

Activation of Pyk2 by Stress Signals and Coupling with JNK Signaling Pathway

G. Tokiwa, * I. Dikic, * S. Lev, J. Schlessinger dagger

The c-Jun amino-terminal kinase (JNK) is activated by various heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors, inflammatory cytokines, and stress signals. Yet, upstream mediators that link extracellular signals with the JNK signaling pathway are currently unknown. The tyrosine kinase Pyk2 was activated by tumor necrosis factor alpha , by ultraviolet irradiation, and by changes in osmolarity. Overexpression of Pyk2 led to activation of JNK, and a dominant-negative mutant of Pyk2 interfered with ultraviolet light- or osmotic shock-induced activation of JNK. Pyk2 represents a cell type-specific, stress-sensitive mediator of the JNK signaling pathway.

G. Tokiwa, I. Dikic, J. Schlessinger, Department of Pharmacology, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA.
S. Lev, SUGEN, 515 Galveston Drive, Redwood City, CA 94063, USA.
*   These authors contributed equally to this report.

dagger    To whom correspondence should be addressed.


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S. Lev, J. Hernandez, R. Martinez, A. Chen, G. Plowman, and J. Schlessinger (1999)
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   Abstract »    Full Text »    PDF »
Adrenomedullin as a Novel Growth-Promoting Factor for Cultured Vascular Smooth Muscle Cells: Role of Tyrosine Kinase-Mediated Mitogen-Activated Protein Kinase Activation.
H. Iwasaki, S. Eguchi, M. Shichiri, F. Marumo, and Y. Hirata (1998)
Endocrinology 139, 3432-3441
   Abstract »    Full Text »    PDF »
Human Immunodeficiency Virus Tat Modulates the Flk-1/KDR Receptor, Mitogen-Activated Protein Kinases, and Components of Focal Adhesion in Kaposi's Sarcoma Cells.
R. K. Ganju, N. Munshi, B. C. Nair, Z.-Y. Liu, P. Gill, and J. E. Groopman (1998)
J. Virol. 72, 6131-6137
   Abstract »    Full Text »    PDF »
Angiotensin II Stimulates p21-Activated Kinase in Vascular Smooth Muscle Cells : Role in Activation of JNK.
U. Schmitz, T. Ishida, M. Ishida, J. Surapisitchat, M. I. Hasham, S. Pelech, and B. C. Berk (1998)
Circ. Res. 82, 1272-1278
   Abstract »    Full Text »    PDF »
Identification of a New Pyk2 Isoform Implicated in Chemokine and Antigen Receptor Signaling.
I. Dikic, I. Dikic, and J. Schlessinger (1998)
J. Biol. Chem. 273, 14301-14308
   Abstract »    Full Text »    PDF »
Signal Transduction and Signal Modulation by Cell Adhesion Receptors: The Role of Integrins, Cadherins, Immunoglobulin-Cell Adhesion Molecules, and Selectins.
A. E. Aplin, A. Howe, S. K. Alahari, and R. L. Juliano (1998)
Pharmacol. Rev. 50, 197-264
   Abstract »    Full Text »    PDF »
The Related Adhesion Focal Tyrosine Kinase (RAFTK) Is Tyrosine Phosphorylated and Participates in Colony-Stimulating Factor-1/Macrophage Colony-Stimulating Factor Signaling in Monocyte-Macrophages.
W. C. Hatch, R. K. Ganju, D. Hiregowdara, S. Avraham, and J. E. Groopman (1998)
Blood 91, 3967-3973
   Abstract »    Full Text »    PDF »
Bruton's Tyrosine Kinase-mediated Interleukin-2 Gene Activation in Mast Cells. DEPENDENCE ON THE c-Jun N-TERMINAL KINASE ACTIVATION PATHWAY.
D. Hata, J. Kitaura, S. E. Hartman, Y. Kawakami, T. Yokota, and T. Kawakami (1998)
J. Biol. Chem. 273, 10979-10987
   Abstract »    Full Text »    PDF »
Fluoroaluminate Induces Activation and Association of Src and Pyk2 Tyrosine Kinases in Osteoblastic MC3T3-E1 Cells.
M. Jeschke, G. J. R. Standke, and M. Susa (1998)
J. Biol. Chem. 273, 11354-11361
   Abstract »    Full Text »    PDF »
Pyk2 is a downstream mediator of the IL-2 receptor-coupled Jak signaling pathway.
T. Miyazaki, A. Takaoka, L. Nogueira, I. Dikic, H. Fujii, S. Tsujino, Y. Mitani, M. Maeda, J. Schlessinger, and T. Taniguchi (1998)
Genes & Dev. 12, 770-775
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Differential Regulation of Pyk2 and Focal Adhesion Kinase (FAK). THE C-TERMINAL DOMAIN OF FAK CONFERS RESPONSE TO CELL ADHESION.
C. Zheng, Z. Xing, Z. C. Bian, C. Guo, A. Akbay, L. Warner, and J.-L. Guan (1998)
J. Biol. Chem. 273, 2384-2389
   Abstract »    Full Text »    PDF »
Regulation of a Calcium-dependent Tyrosine Kinase in Vascular Smooth Muscle Cells by Angiotensin II and Platelet-derived Growth Factor. DEPENDENCE ON CALCIUM AND THE ACTIN CYTOSKELETON.
A. E. Brinson, T. Harding, P. A. Diliberto, Y. He, X. Li, D. Hunter, B. Herman, H. S. Earp, and L. M. Graves (1998)
J. Biol. Chem. 273, 1711-1718
   Abstract »    Full Text »    PDF »
Cell Adhesion Kinase beta  Forms a Complex with a New Member, Hic-5, of Proteins Localized at Focal Adhesions.
M. Matsuya, H. Sasaki, H. Aoto, T. Mitaka, K. Nagura, T. Ohba, M. Ishino, S. Takahashi, R. Suzuki, and T. Sasaki (1998)
J. Biol. Chem. 273, 1003-1014
   Abstract »    Full Text »    PDF »
Functional Significance of Cell Volume Regulatory Mechanisms.
F. LANG, G. L. BUSCH, M. RITTER, H. VOLKL, S. WALDEGGER, E. GULBINS, and D. HAUSSINGER (1998)
Physiol Rev 78, 247-306
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Activation of Protein-tyrosine Kinase Pyk2 Is Downstream of Syk in Fcepsilon RI Signaling.
H. Okazaki, J. Zhang, M. M. Hamawy, and R. P. Siraganian (1997)
J. Biol. Chem. 272, 32443-32447
   Abstract »    Full Text »    PDF »
Cross-talk between Phorbol Ester-mediated Signaling and Tyrosine Kinase Proto-oncogenes. II COMPARISON OF PHORBOL ESTER AND SPHINGOMYELINASE-INDUCED PHOSPHORYLATION OF ErbB2 AND ErbB3.
R. Emkey and C. R. Kahn (1997)
J. Biol. Chem. 272, 31182-31189
   Abstract »    Full Text »    PDF »
Fluid Shear Stress Activation of Focal Adhesion Kinase. LINKING TO MITOGEN-ACTIVATED PROTEIN KINASES.
S. Li, M. Kim, Y.-L. Hu, S. Jalali, D. D. Schlaepfer, T. Hunter, S. Chien, and J. Y-J. Shyy (1997)
J. Biol. Chem. 272, 30455-30462
   Abstract »    Full Text »    PDF »
Signal Transduction Due to HIV-1 Envelope Interactions with Chemokine Receptors CXCR4 or CCR5.
C. B. Davis, I. Dikic, D. Unutmaz, C. M. Hill, J. Arthos, M. A. Siani, D. A. Thompson, J. Schlessinger, and D. R. Littman (1997)
J. Exp. Med. 186, 1793-1798
   Abstract »    Full Text »    PDF »
Tyrosine Phosphorylation of Crk-associated Substrates by Focal Adhesion Kinase. A PUTATIVE MECHANISM FOR THE INTEGRIN-MEDIATED TYROSINE PHOSPHORYLATION OF Crk-ASSOCIATED SUBSTRATES.
K. Tachibana, T. Urano, H. Fujita, Y. Ohashi, K. Kamiguchi, S. Iwata, H. Hirai, and C. Morimoto (1997)
J. Biol. Chem. 272, 29083-29090
   Abstract »    Full Text »    PDF »
Signal Transduction in Human Hematopoietic Cells by Vascular Endothelial Growth Factor Related Protein, a Novel Ligand for the FLT4 Receptor.
J.-F. Wang, R. K. Ganju, Z.-Y. Liu, H. Avraham, S. Avraham, and J. E. Groopman (1997)
Blood 90, 3507-3515
   Abstract »    Full Text »    PDF »
Induction of Apoptosis after Expression of PYK2, a Tyrosine Kinase Structurally Related to Focal Adhesion Kinase.
W.-c. Xiong and J. T. Parsons (1997)
J. Cell Biol. 139, 529-539
   Abstract »    Full Text »    PDF »


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