In addition to notch-1 and APP, RIP of the membrane-anchored carboxyl terminal fragments of the neurogenic signals receptor tyrosine kinases ErbB4 (Ni et al., 2001; Sardi et al., 2006), IGF-1R (McElroy et al., 2007), insulin receptor (Kasuga et al., 2007), L1 (Maretzky et al., 2005b) and E-cadherin (Marambaud et al., 2002) are catalyzed by PS1/γ-secretase. Neuregulin 1 (NRG1)-induced presenilin-dependent ErbB4 nuclear signaling regulates the timing of astrogenesis in the developing brain (Sardi et al., 2006). Upon activation and presenilin-dependent cleavage of ErbB4 juxtamembrane-a (JMa), its intracellular domain (E4ICD) forms a complex with the signaling protein TAB2 and the corepressor N-CoR. This complex translocates to the nucleus of undifferentiated neural precursors and inhibits their differentiation into astrocytes by repressing the transcription of glial genes (Sardi et al., 2006).
