int-3

Ligand for members of the frizzled family of seven transmembrane receptors. Functions in the canonical Wnt signaling pathway that results in activation of transcription factors of the TCF/LEF family. Required for normal gastrulation, formation of the primitive streak, and for the formation of the mesoderm during early embryogenesis. Required for normal formation of the apical ectodermal ridge and for normal embryonic limb development.

The Notch signaling pathway is important for cell-cell communication; it is involved in gene regulation mechanisms that control multiple cell differentiation processes during embryonic and adult life. Notch-4 expression correlates with Ki67. Notch-4 also plays a key role in breast cancer stem-like cells.

Mycophenolic acid (MPA), the active metabolite of the immunosuppressant mycophenolate mofetil (MMF), is primarily metabolized by glucuronidation to a phenolic glucuronide (MPAG) and an acyl glucuronide (AcMPAG). It is known that AcMPAG, which may be an immunotoxic metabolite, is deglucuronidated in human liver. AcMPAG deglucuronidation activity was detected in both human liver cytosol (HLC) and microsomes (HLM). By purification from HLC with column chromatographic purification steps, the enzyme responsible for AcMPAG deglucuronidationis identified as α/β hydrolase domain containing 1 (ABHD1). Recombinant ABHD1 expressed in Sf9 cells efficiently deglucuronidated AcMPAG with a K(m) value of 1.7 ± 1.2 μM, which was similar to those in HLM, HLC, and human liver homogenates (HLH). Immunoblot analysis revealed ABHD1 protein expression in both HLC and HLM. The AcMPAG deglucuronidation by recombinant ABHD1, HLC, and HLH were potently inhibited by AgNO(3), CdCl(2), CuCl(2), PMSF, bis-p-nitrophenylphosphate, and DTNB. The CL(int) value of AcMPAG formation from MPA, which was catalyzed by human UGT2B7, in HLH was increased by 1.8-fold in the presence of PMSF. Thus, human ABHD1 would affect the formation of AcMPAG, the immunotoxic metabolite.

NOTCH4 (Notch Receptor 4) is a Protein Coding gene. Notch4 belongs to a family of transmembrane receptors that play an important role in vascular development and maintenance. The NOTCH4 gene is located at 6p21.3 and is involved in the development and patterning of the central nervous systems. It regulates signaling pathways associated with neuronal maturation, a process involved in the development and patterning of the central nervous system. The NOTCH4 gene has also been identified as a possible susceptibility gene for schizophrenia (SCZ). It is broadly expressed in fat, lung, and other tissues. The NOTCH4 gene, located within the MHC region, is involved in cellular differentiation and has varying effects dependent on tissue type.