Table 1.
Defects in TCR signaling and development in the absence of Lck and/or Fyn.
| Activity/TCR-dependent signaling pathway | Defect in Lck KO?* | Defect in Fyn KO? | Defect in double KO?* | Notes |
|---|---|---|---|---|
| Development through pre-TCR checkpoint | Strong defect, but incomplete | Little or no defect | Complete block at DN3 | Fyn activity in absence of Lck enables some development to proceed but double KO completely abrogates development to SP (Appleby et al., 1992; Molina et al., 1992; Stein et al., 1992; Groves et al., 1996; van Oers et al., 1996a) |
| Development through positive selection checkpoint | Strong defect | Little or no defect | Development blocked before this stage (at DN3) | Fyn activity in absence of Lck is minor (Appleby et al., 1992; Stein et al., 1992) |
| CD3ζ phosphorylation (constitutive) | Minor defect | Minor defect | strong | Either Lck (at normal quantity) or Fyn is sufficient for survival of T cells, but low Lck expression not sufficient (Seddon and Zamoyska, 2002) |
| TCR-stimulated CD3ζ, ZAP70, LAT phosphorylation | Major reduction | Minor defect | Stronger defect than Lck KO | Fyn is not very important (Van Oers et al., 1996b), but it has a minor role (Lovatt et al., 2006; Filby et al., 2007) |
| PLCγ1 phosphorylation | Major defect | Little or no defect | Major defect | Fyn alone cannot transduce signals leading to PLCγ1 activation (Appleby et al., 1992; Stein et al., 1992; Lovatt et al., 2006) |
| DAG production and RasGRP translocation to plasma membrane | Major defect | Little or no defect | Major defect | Lovatt et al. (2006) |
| Ca2+ flux | Major defect | Minor defect | Major defect | Appleby et al. (1992), Lovatt et al. (2006), Stein et al. (1992) |
| Erk pathway activation | Partial defect | Partial defect | Major defect | Both Fyn and Lck are involved in Erk activation. Fyn alone activates Erk by a different pathway than PLCγ1-RasGRP (Lovatt et al., 2006; Filby et al., 2007) |
| PI3K activation | Slight defect | Slight defect | Major defect | Either Fyn and Lyk are sufficient to activate PI3K pathway (Salmond et al., 2009b) |
| Phosphorylation of ribosomal protein S6 | Slight defect | Slight defect | nd | Both Lck and Fyn required for full phosphorylation of rpS6, downstream of Erk and PI3K pathways (Salmond et al., 2009a) |
| Pyk2 phosphorylation | Little or no defect | Major defect | nd | Fyn is required for phosphorylation of the focal adhesion kinase Pyk2 (Qian et al., 1997) |
| Csk binding protein (Cbp/PAG) phosphorylation | nd | Major defect | nd | Fyn is required for activation of Cbp/PAG (Yasuda et al., 2002) |
| Negative feedback on TCR signaling | No defect | KO allows stronger signaling | Filby et al. (2007) |