Details

Autor(en) / Beteiligte

• Oganesian, Anush
• Au, Sandra
• Horst, Jeremy A.
• Holzhausen, Lars C.
• Macy, Athena J.
• Pace, James M.
• Bornstein, Paul

Titel

The NH2-terminal Propeptide of Type I Procollagen Acts Intracellularly to Modulate Cell Function

Ist Teil von

• The Journal of biological chemistry, 2006-12, Vol.281 (50), p.38507-38518

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2006

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• The function of the NH2-terminal propeptide of type I procollagen (N-propeptide) is poorly understood. We now show that a recombinant trimeric N-propeptide interacts with transforming growth factor-β1 and BMP2 and exhibits functional effects in stably transfected cells. The synthesis of N-propeptide by COS-7 cells results in an increase in phosphorylation of Akt and Smad3 and is associated with a marked reduction in type I procollagen synthesis and impairment in adhesion. In C2C12 cells, N-propeptide inhibits the osteoblastic differentiation induced by BMP2. Our data suggest that these effects are mediated by the interaction of N-propeptide with an intracellular receptor in the secretory pathway, because they are not observed when recombinant N-propeptide is added to the culture medium of either COS-7 or C2C12 cells. Both the binding of N-propeptide to cytokines and its functional properties are entirely dependent on the exon 2-encoded globular domain, and a mutation that substitutes a serine for a highly conserved cysteine in exon 2 abolishes its function. Our findings suggest that N-propeptide performs an important feedback regulatory function and provides a rationale for the prominence of a homotrimeric form of type I procollagen (α1 trimer) during vertebrate development.