© The Rockefeller University Press,
0021-9525/1999//1561 $5.00
The Journal of Cell Biology, Volume 147, Number 7,
, 1999 1561-1568
Bifurcation of Cell Migratory and Proliferative Signaling by the Adaptor Protein Shc
Lila R. Collinsa,
William A. Rickettsb,
Linda Yeha, and
David Cheresha
a Department of Immunology and Department of Vascular Biology, The Scripps Research Institute, La Jolla, California 92037
b Isis Pharmaceuticals, Carlsbad, California 92008
Departments of Immunology and Vascular Biology, IMM24, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037.(858) 784-8926(858) 784-8281
cheresh{at}scripps.edu
Cytokines and extracellular matrix proteins initiate signaling cascades that regulate cell migration and proliferation. Evidence is provided that the adaptor protein Shc can differentially regulate these processes. Specifically, under growth factor–limiting conditions, Shc stimulates haptotactic cell migration without affecting anchorage-dependent proliferation. However, when growth factors are present, Shc no longer influences cell migration; rather, Shc is crucial for DNA synthesis. Mutational analysis of Shc demonstrates that, while tyrosine phosphorylation is required for both DNA synthesis and cell migration, the switch in Shc signaling is associated with differential use of Shc's phosphotyrosine interacting domains; the PTB domain regulates haptotaxis, while the SH2 domain is selectively required for proliferation.
Key Words: Shc cell migration mitogenesis SH2 PTB
© 1999 The Rockefeller University Press
Abbreviations used in this paper: ANOVA, analysis of variance; BrdU, bromodeoxyuridine; CH, collagen homology; ECM, extracellular matrix; ERK, extracellular signal-related kinase; FAK, focal adhesion kinase; SH2, Src homology 2; PTB, phosphotyrosine binding.

CiteULike
Complore
Connotea
Del.icio.us
Digg
Facebook
Reddit
Technorati
Twitter What's this?
This article has been cited by other articles:
-
Alam, S. M., Rajendran, M., Ouyang, S., Veeramani, S., Zhang, L., Lin, M.-F.
(2009). A novel role of Shc adaptor proteins in steroid hormone-regulated cancers. Endocr Relat Cancer
16: 1-16
[Abstract]
[Full Text]
-
Northey, J. J., Chmielecki, J., Ngan, E., Russo, C., Annis, M. G., Muller, W. J., Siegel, P. M.
(2008). Signaling through ShcA Is Required for Transforming Growth Factor {beta}- and Neu/ErbB-2-Induced Breast Cancer Cell Motility and Invasion. Mol. Cell. Biol.
28: 3162-3176
[Abstract]
[Full Text]
-
Liu, H., Radisky, D. C., Nelson, C. M., Zhang, H., Fata, J. E., Roth, R. A., Bissell, M. J.
(2006). Mechanism of Akt1 inhibition of breast cancer cell invasion reveals a protumorigenic role for TSC2.. Proc. Natl. Acad. Sci. USA
103: 4134-4139
[Abstract]
[Full Text]
-
Prasad, N. K., Decker, S. J.
(2005). SH2-containing 5'-Inositol Phosphatase, SHIP2, Regulates Cytoskeleton Organization and Ligand-dependent Down-regulation of the Epidermal Growth Factor Receptor. J. Biol. Chem.
280: 13129-13136
[Abstract]
[Full Text]
-
Audero, E., Cascone, I., Maniero, F., Napione, L., Arese, M., Lanfrancone, L., Bussolino, F.
(2004). Adaptor ShcA Protein Binds Tyrosine Kinase Tie2 Receptor and Regulates Migration and Sprouting but Not Survival of Endothelial Cells. J. Biol. Chem.
279: 13224-13233
[Abstract]
[Full Text]
-
Vindis, C., Cerretti, D. P., Daniel, T. O., Huynh-Do, U.
(2003). EphB1 recruits c-Src and p52Shc to activate MAPK/ERK and promote chemotaxis. JCB
162: 661-671
[Abstract]
[Full Text]
-
Prasad, N., Topping, R. S., Decker, S. J.
(2002). Src family tyrosine kinases regulate adhesion-dependent tyrosine phosphorylation of 5'-inositol phosphatase SHIP2 during cell attachment and spreading on collagen I. J. Cell Sci.
115: 3807-3815
[Abstract]
[Full Text]
-
Eliceiri, B. P.
(2001). Integrin and Growth Factor Receptor Crosstalk. Circ. Res.
89: 1104-1110
[Abstract]
[Full Text]
-
Mariotti, A., Kedeshian, P. A., Dans, M., Curatola, A. M., Gagnoux-Palacios, L., Giancotti, F. G.
(2001). EGF-R signaling through Fyn kinase disrupts the function of integrin {alpha}6{beta}4 at hemidesmosomes: role in epithelial cell migration and carcinoma invasion. JCB
155: 447-458
[Abstract]
[Full Text]
-
Yano, H., Uchida, H., Iwasaki, T., Mukai, M., Akedo, H., Nakamura, K., Hashimoto, S., Sabe, H.
(2000). Paxillin alpha and Crk-associated substrate exert opposing effects on cell migration and contact inhibition of growth through tyrosine phosphorylation. Proc. Natl. Acad. Sci. USA
97: 9076-9081
[Abstract]
[Full Text]
-
Hermanns, H. M., Radtke, S., Schaper, F., Heinrich, P. C., Behrmann, I.
(2000). Non-redundant Signal Transduction of Interleukin-6-type Cytokines. THE ADAPTER PROTEIN Shc IS SPECIFICALLY RECRUITED TO THE ONCOSTATIN M RECEPTOR. J. Biol. Chem.
275: 40742-40748
[Abstract]
[Full Text]
-
Dans, M., Gagnoux-Palacios, L., Blaikie, P., Klein, S., Mariotti, A., Giancotti, F. G.
(2001). Tyrosine Phosphorylation of the beta 4 Integrin Cytoplasmic Domain Mediates Shc Signaling to Extracellular Signal-regulated Kinase and Antagonizes Formation of Hemidesmosomes. J. Biol. Chem.
276: 1494-1502
[Abstract]
[Full Text]