Secretion of hepatoma-derived growth factor is regulated by N-terminal processing
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Ketan Thakar
Abstract
Hepatoma-derived growth factor (HDGF) was first purified as a growth factor secreted by hepatoma cells. It promotes angiogenesis and has been related to tumorigenesis. To date, little is known about the molecular mechanisms of HDGF functions and especially its routes or regulation of secretion. Here we show that secretion of HDGF requires the N-terminal 10 amino acids and that this peptide can mediate secretion of other proteins, such as enhanced green fluorescent protein, if fused to their N-terminus. Our results further demonstrate that cysteine residues at positions 12 and 108 are linked via an intramolecular disulfide bridge. Surprisingly, phosphorylation of serine 165 in the C-terminal part of HDGF plays a critical role in the secretion process. If this serine is replaced by alanine, the N-terminus is truncated, the intramolecular disulfide bridge is not formed and the protein is not secreted. In summary, these observations provide a model of how phosphorylation, a disulfide bridge and proteolytic cleavage are involved in HDGF secretion.
©2010 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Minireview
- Physiology and pathophysiology of the RANKL/RANK system
- Genes and Nucleic Acids
- Murine aldo-keto reductase family 1 subfamily B: identification of AKR1B8 as an ortholog of human AKR1B10
- Characterization of plant miRNAs and small RNAs derived from potato spindle tuber viroid (PSTVd) in infected tomato
- Protein Structure and Function
- Characterization of a mutant R11H αB-crystallin associated with human inherited cataract
- Secretion of hepatoma-derived growth factor is regulated by N-terminal processing
- Twin arginine translocation (Tat)-dependent protein transport: the passenger protein participates in the initial membrane binding step
- Kinetic and structural characterization of bacterial glutaminyl cyclases from Zymomonas mobilis and Myxococcus xanthus
- Membranes, Lipids, Glycobiology
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- Molecular Medicine
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- Cell Biology and Signaling
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- Increase of SARS-CoV 3CL peptidase activity due to macromolecular crowding effects in the milieu composition
- Pharmacological and genetic evidence that cathepsin B is not the physiological activator of rodent prorenin
- Acknowledgement
- Acknowledgement
