Hi everyone,

I am trying to design a hormone with a signaling peptide so it is secreted out of the hepatocytes into the media/plasma. The problem is, the hormone is expressed by a different type of cells and not by the hepatocytes. When I add various liver-expressed signaling peptides (e.g. albumin, fibronectin, etc.) to the hormone sequence and check the cleavage site in SignalP 6.0, it always predicts cleavage be in the wrong place close to the active site of the hormone. I am thinking of using a native signaling peptide for this specific protein, because SignalP 6.0 shows it cleaved off in the correct place. The problem is, I do not know if the liver cells will recognise the native signaling peptide and correctly secrete it out of hepatocytes.

Could you please suggest if the idea will work and share with me some research papers that discuss how secreted proteins are excreted (molecular mechanism) as I am currently struggling to find any suitable ones. Thank you!