Identification of a family of fatty-acid-speciated sonic hedgehog proteins, whose members display differential biological properties.
Hedgehog (HH) proteins are proteolytically processed into a biologically active form that is covalently modified by cholesterol and palmitate. However, most studies of HH biogenesis have characterized protein from cells in which HH is overexpressed. We purified Sonic Hedgehog (SHH) from cells expressing physiologically relevant levels and showed that it was more potent than SHH isolated from overexpressing cells. Furthermore, the SHH in our preparations was modified with a diverse spectrum of fatty acids on its amino termini, and this spectrum of fatty acids varied dramatically depending on the growth conditions of the cells. The fatty acid composition of SHH affected its trafficking to lipid rafts as well as its potency. Our results suggest that HH proteins exist as a family of diverse lipid-speciated proteins that might be altered in different physiological and pathological contexts in order to regulate distinct properties of HH proteins.
Molecular Oncology Program, The DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida 33136.|The Sheila and David Fuente Graduate Program in Cancer Biology, University of Miami Miller School of Medicine, Miami, Florida 33136.
Jun
J
Long
Molecular Oncology Program, The DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida 33136.|Program in Experimental and Molecular Medicine, Dartmouth Medical School, Hanover, New Hampshire 03755.
Robert
R
Tokhunts
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado 80309.
William M
WM
Old
Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309.
Stephane
S
Houel
Molecular Oncology Program, The DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida 33136.
Jezabel
J
Rodgriguez-Blanco
Molecular Oncology Program, The DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida 33136.
Samer
S
Singh
Molecular Oncology Program, The DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida 33136.|Program in Experimental and Molecular Medicine, Dartmouth Medical School, Hanover, New Hampshire 03755.
Neal
N
Schilling
Molecular Oncology Program, The DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida 33136.|Sylvester Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida 33136.|Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, Florida 33136.
Anthony
A
J Capobianco
Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309.|Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado 80309.
Natalie G
NG
Ahn
Molecular Oncology Program, The DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida 33136.|Sylvester Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida 33136.|Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, Florida 33136.
David J
DJ
Robbins
D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D002645:Chickens / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D010455:Peptides / Q000032:analysis / Q000737:chemistry; D053719:Tandem Mass Spectrometry
D005227:Fatty Acids; D053823:Hedgehog Proteins; D010455:Peptides