Dkk-1

O94907

DKK-1 is a member of the DKK protein family which also includes DKK-2, DKK-3 and DKK-4. DKK-1 was originally identified as a Xenopus head forming molecule that behaves as an antagonist for Wnt signaling. Subsequent studies have shown that DKK-1 and DKK-4 play an important regulatory role in the Wnt /ß-catenin signaling pathway by forming inhibitory complexes with LDL receptor-related proteins 5 and 6 (LRP5 and LRP6), which are essential components of the Wnt/ßcatenin signaling system. LPR5 and LPR6 are single-pass transmembrane proteins that appear to act as co-receptors for Wnt ligands involved in the Wnt/ßcatenin signaling cascade. It has been suggested that by inhibiting Wnt/ß-catenin signaling, which is essential for posterior patterning in vertebrates, DKK-1 permits anterior development. This notion is supported by the finding that mice deficient of DKK-1 expression lack head formation and die during embryogenesis. Recombinant human DKK-1 expressed in human 293 cells is a 35-40 kDa glycoprotein containing 235 amino-acid residues.

235

NM_012242.2

TLNSVLNSNA IKNLPPPLGG AAGHPGSAVS AAPGILYPGG NKYQTIDNYQ PYPCAEDEEC GTDEYCASPT RGGDAGVQIC LACRKRRKRC MRHAMCCPGN YCKNGICVSS DQNHFRGEIE ETITESFGND HSTLDGYSRR TTLSSKMYHT KGQEGSVCLR SSDCASGLCC ARHFWSKICK PVLKEGQVCT KHRRKGSHGL EIFQRCYCGE GLSCRIQKDH HQASNSSRLH TC

Dickkopf-related protein-1, Dickkopf-1, SK