Role of Shc in T-cell development and function.
Shc is a prototype adapter protein that is expressed from the earliest stages of T-cell development. Shc becomes rapidly tyrosine phosphorylated after T-cell receptor (TCR) engagement. Expression of dominant negative forms of Shc in T-cell lines had also suggested a role for this adapter downstream of the TCR. However, until recently, the relative significance of Shc compared to several other adapters in T cells was unclear. Mice lacking Shc expression specifically in the T-cell lineage together with inducible expression of dominant negative Shc in transgenic mice have revealed an essential and nonredundant role for Shc in thymic T-cell development. Functional defects in a Jurkat T-cell line lacking Shc expression also suggest a role for Shc in mature T-cell functions. While the requirement of Shc in T-cell signaling is now established, precisely what signaling pathways downstream of Shc make this adapter unique are less clear. Although the Shc-mediated activation of the extracellular signal regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) pathway could be one component, Shc likely signals to other pathways in T cells that are not yet discovered. A better molecular understanding of Shc function in the future could provide insights into how multiple adapters coordinate the various outcomes downstream of the TCR.
Zhang
Li
L
Department of Microbiology and the Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908, USA.
Lorenz
Ulrike
U
Ravichandran
Kodi S
KS
D000818:Animals; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*
D015513:Oncogene Proteins; C401583:SHC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D055765:Shc Signaling Adaptor Proteins