| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
(Received for publication, May 2, 1996, and in revised form, June 24, 1996)
From the Program in Molecular Medicine and Department of Cell
Biology, University of Massachusetts Medical School,
Worcester, Massachusetts 01655
The proto-oncogene c-Cbl was originally
identified as a cellular homologue of the transforming protein
expressed by the murine Cas NS-1 retrovirus. The full-length c-Cbl
protein is a predominantly cytoplasmic protein, abundant in lymphoid
cells, and potentially involved in signal transduction in several cell
types. The specific signal transduction pathways in which c-Cbl
participates, and its precise role in these pathways, are unclear.
Previous studies from our laboratory have shown that c-Cbl is the
predominant tyrosine-phosphorylated protein bound to the p85 subunit of
phosphatidylinositol (PI) 3-kinase on T lymphocyte and B lymphocyte
activation. To further understand the properties of c-Cbl and the
significance of its interactions with PI 3-kinase, we have further
studied the cellular biological and biochemical responses of c-Cbl to
stimulation in lymphoid cells. We show that stimulation induces the
association of a highly tyrosine-phosphorylated pool of c-Cbl with
lymphocyte membranes and with a detergent-insoluble particulate
fraction. Immunoprecipitation of c-Cbl from subcellular fractions
reveals that p85 is predominantly associated with the c-Cbl pool
recovered from the membrane fraction, despite the fact that this pool
represents a small amount of total cellular c-Cbl. The formation of
c-Cbl·PI 3-kinase complexes on lymphocyte membranes did not depend on
the catalytic activity of PI 3-kinase since it was unaltered by the
treatment of cells with wortmannin prior to stimulation. Interestingly,
c-Cbl tyrosine phosphorylation and the formation of c-Cbl·PI 3-kinase
complexes were also observed in a mutant Jurkat cell line, JCaM1.6,
lacking p56lck expression. Because p56lck is critical
for mitogenic signal transduction in response to T cell receptor
activation, our results suggest that the activation of c-Cbl and the
formation of c-Cbl·PI 3-kinase complexes occur upstream or
independently of mitogenic signal transduction pathways in T cells.
This article has been cited by other articles:
|
|
 |
|
  K. Haglund, I. Ivankovic-Dikic, N. Shimokawa, G. D. Kruh, and I. Dikic Recruitment of Pyk2 and Cbl to lipid rafts mediates signals important for actin reorganization in growing neurites J. Cell Sci., May 15, 2004; 117(12): 2557 - 2568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Munoz, M.-d.-C. Navarro, E. J. Pavon, J. Salmeron, F. Malavasi, J. Sancho, and M. Zubiaur CD38 Signaling in T Cells Is Initiated within a Subset of Membrane Rafts Containing Lck and the CD3-{zeta} Subunit of the T Cell Antigen Receptor J. Biol. Chem., December 12, 2003; 278(50): 50791 - 50802. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Y. Hawash, K. P. Kesavan, A. I. Magee, R. L. Geahlen, and M. L. Harrison The Lck SH3 Domain Negatively Regulates Localization to Lipid Rafts through an Interaction with c-Cbl J. Biol. Chem., February 8, 2002; 277(7): 5683 - 5691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Clague and S. Urbe The interface of receptor trafficking and signalling J. Cell Sci., January 9, 2001; 114(17): 3075 - 3081. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Lazaar, V. P. Krymskaya, and S. K. P. Das VCAM-1 Activates Phosphatidylinositol 3-Kinase and Induces p120Cbl Phosphorylation in Human Airway Smooth Muscle Cells J. Immunol., January 1, 2001; 166(1): 155 - 161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-i. Honda, T. Suzuki, H. Kono, M. Okada, T. Yamamoto, C. Ra, Y. Morita, and K. Yamamoto Sequential Requirements of the N-Terminal Palmitoylation Site and SH2 Domain of Src Family Kinases in the Initiation and Progression of Fcvarepsilon RI Signaling Mol. Cell. Biol., March 1, 2000; 20(5): 1759 - 1771. [Abstract] [Full Text]
|
|
|
|
|
|
H. Gary-Gouy, P. Bruhns, C. Schmitt, A. Dalloul, M. Daeron, and G. Bismuth The Pseudo-immunoreceptor Tyrosine-based Activation Motif of CD5 Mediates Its Inhibitory Action on B-cell Receptor Signaling J. Biol. Chem., January 7, 2000; 275(1): 548 - 556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. O. Beitz, D. A. Fruman, T. Kurosaki, L. C. Cantley, and A. M. Scharenberg SYK Is Upstream of Phosphoinositide 3-Kinase in B Cell Receptor Signaling J. Biol. Chem., November 12, 1999; 274(46): 32662 - 32666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Fernandez, M. P. Czech, and H. Meisner Role of Protein Kinase C in Signal Attenuation following T Cell Receptor Engagement J. Biol. Chem., July 16, 1999; 274(29): 20244 - 20250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. B. F. Thien, D. D. L. Bowtell, and W. Y. Langdon Perturbed Regulation of ZAP-70 and Sustained Tyrosine Phosphorylation of LAT and SLP-76 in c-Cbl-Deficient Thymocytes J. Immunol., June 15, 1999; 162(12): 7133 - 7139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Saci, S. Pain, F. Rendu, and C. Bachelot-Loza Fc Receptor-mediated Platelet Activation Is Dependent on Phosphatidylinositol 3-Kinase Activation and Involves p120cbl J. Biol. Chem., January 22, 1999; 274(4): 1898 - 1904. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hunter, E. A. Burton, S. C. Wu, and S. M. Anderson Fyn Associates with Cbl and Phosphorylates Tyrosine 731 in Cbl, A Binding Site for Phosphatidylinositol 3-Kinase J. Biol. Chem., January 22, 1999; 274(4): 2097 - 2106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Okazaki, N. Chikatsu, M. Nakatsu, Y. Takeuchi, M. Ajima, J. Miki, T. Fujita, M. Arai, Y. Totsuka, K. Tanaka, et al. A Novel Activating Mutation in Calcium-Sensing Receptor Gene Associated with a Family of Autosomal Dominant Hypocalcemia J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 363 - 366. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. Naramura, H. K. Kole, R.-J. Hu, and H. Gu Altered thymic positive selection and intracellular signals in Cbl-deficient mice PNAS, December 22, 1998; 95(26): 15547 - 15552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. W. McVicar, L. S. Taylor, P. Gosselin, J. Willette-Brown, A. I. Mikhael, R. L. Geahlen, M. C. Nakamura, P. Linnemeyer, W. E. Seaman, S. K. Anderson, et al. DAP12-mediated Signal Transduction in Natural Killer Cells. A DOMINANT ROLE FOR THE Syk PROTEIN-TYROSINE KINASE J. Biol. Chem., December 4, 1998; 273(49): 32934 - 32942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Feshchenko, W. Y. Langdon, and A. Y. Tsygankov Fyn, Yes, and Syk Phosphorylation Sites in c-Cbl Map to the Same Tyrosine Residues That Become Phosphorylated in Activated T Cells J. Biol. Chem., April 3, 1998; 273(14): 8323 - 8331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Rellahan, L. J. Graham, B. Stoica, K. E. DeBell, and E. Bonvini Cbl-mediated Regulation of T Cell Receptor-induced AP1 Activation. IMPLICATIONS FOR ACTIVATION VIA THE Ras SIGNALING PATHWAY J. Biol. Chem., December 5, 1997; 272(49): 30806 - 30811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Fitzer-Attas, D. G. Schindler, T. Waks, and Z. Eshhar Direct T Cell Activation by Chimeric Single Chain Fv-Syk Promotes Syk-Cbl Association and Cbl Phosphorylation J. Biol. Chem., March 28, 1997; 272(13): 8551 - 8557. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ojaniemi, S. S. Martin, F. Dolfi, J. M. Olefsky, and K. Vuori The Proto-oncogene Product p120cbl Links c-Src and Phosphatidylinositol 3'-Kinase to the Integrin Signaling Pathway J. Biol. Chem., February 7, 1997; 272(6): 3780 - 3787. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Hartley and G. M. Cooper Direct Binding and Activation of STAT Transcription Factors by the Herpesvirus saimiri Protein Tip J. Biol. Chem., May 26, 2000; 275(22): 16925 - 16932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Pedraza-Alva, S. Sawasdikosol, Y. C. Liu, L. B. Merida, M. E. Cruz-Munoz, F. Oceguera-Yanez, S. J. Burakoff, and Y. Rosenstein Regulation of Cbl Molecular Interactions by the Co-receptor Molecule CD43 in Human T Cells J. Biol. Chem., January 5, 2001; 276(1): 729 - 737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Hamilton, K. M. Miller, K. M. Helm, W. Y. Langdon, and S. M. Anderson Suppression of Apoptosis Induced by Growth Factor Withdrawal by an Oncogenic Form of c-Cbl J. Biol. Chem., March 16, 2001; 276(12): 9028 - 9037. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
