The production of 53-55-kDa isoforms is not required for rat L-histidine decarboxylase activity.
Post-translational processing of the histamine-producing enzyme, L-histidine decarboxylase (HDC), leads to the formation of multiple carboxyl-truncated isoforms. Nevertheless, it has been widely reported that the mature catalytically active dimer is dependent specifically on the production of carboxyl-truncated 53-55-kDa monomers. Here we use transiently transfected COS-7 cells to study the properties of carboxyl-truncated rat HDC isoforms in the 52-58-kDa size range. Amino acid sequences important for the production of a 55-kDa HDC isoform were identified by successive truncations through amino acids 502, 503, and 504. Mutating this sequence in the full-length protein prevented the production of 55-kDa HDC but did not affect enzymatic activity. Further truncations to amino acid 472 generated an inactive 53-kDa HDC isoform that was degraded by the proteasome pathway. These results suggested that processed isoforms, apart from 53-55-kDa ones, contribute toward histamine biosynthesis in vivo. This was confirmed in physiological studies where regulated increases in HDC activity were associated with the expression of isoforms that were greater than 55 kDa in size. We provide evidence to show that regulation of HDC expression can be achieved by the differential production or differential stabilization of multiple enzyme isoforms.
Fleming
John V
JV
University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Wang
Timothy C
TC
D000818:Animals; D019556:COS Cells; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005215:Fasting; D006640:Histidine Decarboxylase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D016297:Mutagenesis, Site-Directed; D011493:Protein Kinase C / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000737:chemistry; D014020:Tissue Extracts / Q000737:chemistry
D007527:Isoenzymes; D014020:Tissue Extracts; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D006640:Histidine Decarboxylase