Jan Hofsteenge
Jan Hofsteenge
Molecular and functional aspects of co- and posttranslational protein modifications
Modulation of protein function by covalent modification is of increasing importance as a factor in disease and as a therapeutic target. The discovery of new protein modifications and their function remains a challenge. Using protein/peptide purification and mass spectrometry as well as molecular and cell biology techniques, we focus on two unique forms of glycosylation in secreted proteins, C-mannosylation of tryptophan and O-fucosylation of serine or threonine residues. About 50 examples of the former modification are known, in organisms ranging from C. elegans to man. We are studying enzymes involved in the process and analysing specific proteins lacking the modification. Of the two kinds of O-fucose-linked polysaccharides known, O-linked tetrasaccharide appears to function in intercellular signalling. We have found the first protein containing the product of the second pathway, i.e. Glc-Fuc-O-Ser/Thr and are seeking its function.
Gonzalez de Peredo A, Klein D, Macek B, Hess D, Peter-Katalinic J, Hofsteenge (2002) C-Mannosylation and O-fucosylation of thrombospondin type 1 repeats
Cell Proteomics 1:11-18Hofsteenge J, Müller DR, de Beer T, Löffler A, Richter WJ, Vliegenthart JFG (1994) New type of linkage between a carbohydrate and a protein: C- glycosylation of a specific tryptophan residue in human RNase Us
Biochemistry 33:13524-13530Krieg J, Hartmann S, Vicentini A, Gläsner W, Hess D, Hofsteenge J (1998) The recognition signal for C-mannosylation of Trp-7 in RNase 2 consists of the sequence Trp-x-x-Trp
Mol Biol Cell 9:301-309Furmanek A, Hess D, Rogniaux H, Hofsteenge J (2003) The WSAWS motif is C-hexosylated in a soluble form of the erythropoietin receptor
Biochemistry 42:8452-8458Zanetta JP, Pons A, Richet C, Huet G, Timmerman P, Leroy Y, Bohin A, Bohin JP, Trinel PA, Poulain D, Hofsteenge J (2004) Quantitative gas chromatography/mass spectrometry determination of C-mannosylation of tryptophan residues in glycoproteins
Anal Biochem 329:199-206Doucey MA, Hess D, Cacan R, Hofsteenge J (1998) Protein C-mannosylation is enzyme-catalysed and uses dolichyl-phosphate-mannose as a precursor
Mol Biol Cell 9:291-300Hartmann S, Hofsteenge J (2000) Properdin, the positive regulator of complement, is highly C-mannosylated
J Biol Chem 275:28569-28574Kozma K, Keusch JJ, Hegemann B, Lutter KB, Klein D, Hess D, Haltiwanger RS, Hofsteenge J (2006) Identification and characterization of a beta 1,3-glucosyltransferase that synthesizes the Glc-beta 1,3-Fuc disaccharide on thrombospondin type 1 repeats
J Biol Chem 281:36742-36751Hess D, Keusch JJ, Lesnik Oberstein SA, Hennekam RC, Hofsteenge J (2008) Peters plus syndrome is a new congenital disorder of glycosylation and involves defective O-glycosylation of thrombospondin type 1 repeats
J Biol Chem. 2008 Mar 21;283(12):7354-60Macek B, Hofsteenge J, Peter-Katalinic J (2001) Direct determination of glycosylation sites in O-fucosylated glycopeptides using nano-electrospray quadrupole time-of-flight mass spectrometry
Rapid Commun Mass Spectrom 15:771-777