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) |