基因表达的改变是T细胞获得充分增殖能力和产生效应细胞因子所必需的。特别是有三种转录因子在tcr刺激的基因表达变化中发挥关键作用，即NFkappaB、NFAT和AP-1。NFkappaB激活的一个关键步骤是PRKCQ的刺激和转运。影响PRKCQ激活的关键因素是PI3K。PI3K通过位于p85亚基上的两个SH2结构域与CD28上的磷酸化酪氨酸相互作用而转位到质膜(步骤24)。PI3K的p110亚基磷酸化PIP2的肌醇环，生成PIP3(步骤25)。PTEN催化PIP3到PIP2的反向脱磷酸化过程(步骤27)。PIP3也可能被磷酸酶SHIP去磷酸化生成pi -3,4- p2(步骤26)。PIP3和pi -3,4- p2作为PDK1(步骤28)和AKT(步骤29)的PH结构域的结合位点。PKB在PI3K刺激下被PDK1激活(步骤30)。 PDK1 has an essential role in regulating the activation of PRKCQ and recruitment of CBM complex to the immune synapse. PRKCQ is a member of novel class (DAG dependent, Ca++ independent) of PKC and the only member known to translocate to this synapse. Prior to TCR stimulation PRKCQ exists in an inactive closed conformation. TCR signals stimulate PRKCQ (step 31) and release DAG molecules. Subsequently, DAG binds to PRKCQ via the C1 domain and undergoes phosphorylation on tyrosine 90 by LCK to attain an open conformation (step 32). PRKCQ is further phosphorylated by PDK1 on threonine 538 (step 33). This step is critical for PKC activity. CARMA1 translocates to the plasma membrane following the interaction of its SH3 domain with the 'PxxP' motif on PDK1 (step 34). CARMA1 is phosphorylated by PKC-theta on residue S552 (step 35), leading to the oligomerization of CARMA1. This complex acts as a scaffold, recruiting BCL10 to the synapse by interacting with their CARD domains (step 36). BCL10 undergoes phosphorylation mediated by the enzyme RIP2 (step 37). Activated BCL10 then mediates the ubiquitination of IKBKG by recruiting MALT1 and TRAF6. MALT1 binds to BCL10 with its Ig-like domains and undergoes oligomerization (step 38). TRAF6 binds to the oligomerized MALT1 and also undergoes oligomerization (step 39). Oligomerized TRAF6 acts as a ubiquitin-protein ligase, catalyzing auto-K63-linked polyubiquitination (step 40). This K-63 ubiquitinated TRAF6 activates MAP3K7 kinase bound to TAB2 (step 41) and also ubiquitinates IKBKG in the IKK complex (step 44). MAP3K7 undergoes autophosphorylation on residues T184 and T187 and gets activated (step 42). Activated MAP3K7 kinase phosphorylates IKBKB on residues S177 and S181 in the activation loop and activates the IKK kinase activity (step 43). IKBKB phosphorylates the NFKBIA bound to the NFkappaB heterodimer, on residues S19 and S23 (step 45) and directs NFKBIA to 26S proteasome degradation (step 47). The NFkappaB heterodimer with a free NTS sequence finally migrates to the nucleus to regulate gene transcription (step 46).