Bifurcation of cell migratory and proliferative signaling by the adaptor protein Shc.
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.
Collins
L R
LR
Department of Immunology and Department of Vascular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Ricketts
W A
WA
Yeh
L
L
Cheresh
D
D
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D019556:COS Cells; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D004261:DNA Replication / Q000502:physiology; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D008938:Mitosis / Q000235:genetics; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014162:Transfection; D014407:Tumor Cells, Cultured; D014443:Tyrosine
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D006133:Growth Substances; D011506:Proteins; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014443:Tyrosine