The role of Tec family kinases in T cell development and function.
Three members of the Tec family kinases, Itk, Rlk and Tec, have been implicated in signaling downstream of the T cell receptor (TCR). The activity of these kinases in T cells has been shown to be important for the full activation of phospholipase C-gamma1 (PLC-gamma1). Disruption of Tec family signaling in Itk-/- and Rlk-/-Itk-/- mice has multiple effects on T cell development, cytokine production and T-helper cell differentiation. Furthermore, mice possessing mutations in signaling molecules upstream of PLC-gamma1, such as Src homology 2 (SH2) domain-containing phosphoprotein of 76 kDa (SLP-76), linker for activation of T cells (LAT) and Vav1, or in members of the nuclear factor for activated T cells (NFAT) family of transcription factors, which are downstream of PLC-gamma1, have been found to have similar phenotypes to Tec family-deficient mice, emphasizing the importance of this pathway in regulating T cell activation, differentiation and homeostasis.
Lucas
Julie A
JA
University of Massachussets Medical School Department of Pathology, Worcester, MA 01655, USA.
Miller
Andrew T
AT
Atherly
Luana O
LO
Berg
Leslie J
LJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D051966:Phospholipase C gamma; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma