Wnt-Frizzled signaling is important for early development, regulating cell fate, polarity, differentiation, and migration. The frizzled gene, originally identified in Drosophila, is involved in the development of tissue polarity. The Frizzled proteins contain seven transmembrane domains, a cysteine-rich domain in the extracellular region and a C-terminal Ser/Thr-xxx-Val motif, and they function as receptors for Wnt. Human Frizzled-2 (FZD2) is expressed in adult heart and fetal brain, lung and kidney. FZD2 activation leads to the release of beta/gamma subunit complexes from heterotrimeric G-proteins (presumably Gao and Gat) to activate phospholipase C and other effectors to stimulate a mobilization of intracellular Ca++. This does not involve the activation of the canonical WNT-beta-catenin pathway. FZD2 can also signal via the G-protein Gt2, transducin, a G-protein prominent in photo-transduction in the eye, to cyclic GMP phosphodiesterase. The calculated molecular weight of human FZD2 is ~63kD (length = 565aa) or ~71kD (length = 641aa). The observed molecular weight of ~ 85kD may be due to post-translational modifications such as glycosylation, which is predicted in the aa sequence.
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