Recombinant Human IGFBP-4 Protein, CF Best Seller

IGFBP-4 (insulin-like growth factor binding protein 4) is member of the IGFBP family of structurally similar secreted glycoproteins that maintain IGF-I and IGF-II in the circulation and direct them to their target tissues (1, 2). Human IGFBP-4 cDNA encodes 258 amino acids (aa) that include a 21 aa signal peptide and a 237 aa cysteine-rich mature protein that contains an N-terminal IGFBP domain, a linker sequence, and a C-terminal thyroglobulin domain. Mature human IGFBP-4 shares 91% aa sequence identity with mouse and rat IGFBP-4, and 97% with canine, bovine, ovine and porcine IGFBP-4. Both domains interact with IGFs, although the N‑terminal domain is primary (2). The linker contains a cleavage site that is accessible by PAPP-A (pregnancy-associated plasma protein A) when IGFs are bound (2, 3). IGFBP-4 fragments detected in the plasma of pregnant women have lowered affinity for IGFs, thus upregulating IGF bioavailability for receptor binding (2). Unlike other family members, IGFBP-4 does not interact with the extracellular matrix or translocate to the nucleus (2). Like other family members, it is expressed early in development and has both IGF-dependent and -independent activities (2, 4). IGFBP-4 expression in mesenchymal stem cells is upregulated by the cardiac transcription factor GATA-4 (5). It then enhances cardiomyocyte differentiation by interacting with Frizzled and LRP proteins, inhibiting canonical Wnt signaling (6, 7). IGF can sequester IGFBP-4 when present, inhibiting its ability to support cardiomyocyte differentiation (3, 4). IGFBP-4 is also upregulated in osteoblasts in response to estrogen (8). Intact or proteolytically cleaved IGFBP-4 may either promote or inhibit cancer cell growth, motility and invasion depending on cell type, tissue and stage of the cancer (9-11). It is shown to inhibit IGF-1- or FGF-2-induced angiogenesis, but not that induced by VEGF (10).