Biomedical subjects

K Heidrich

Publications and source records attributed to K Heidrich.

4 recordsLinked to original sources

PubMed2000

Interleukin-6 signal transduction and lymphocyte function.

Interleukin-6 (IL-6) is a pleiotropic cytokine that acts on a wide variety of cell types. It has important regulatory functions in the immune system, is a mediator of the acute-phase response, and is involved in the regulation of differentiation, proliferation, and survival of target cells. A major signal transduction pathway for IL-6 involves activation of JAK kinases and the transcription factor Stat3. In addition, a great many of other signalling pathways are induced. Stat3 has been shown to be a central player of IL-6 signalling in many systems whereas the functions of most other IL-6-activated pathways are not yet understood. In this review, we discuss the current knowledge on IL-6 functions in the immune system, IL-6 signal transduction, and its significance for lymphocyte function.

Animals↗

PubMed1998

Hexokinase 2 from Saccharomyces cerevisiae: regulation of oligomeric structure by in vivo phosphorylation at serine-14.

Homodimeric hexokinase 2 from Saccharomyces cerevisiae is known to have two sites of phosphorylation: for serine-14 the modification in vivo increases with glucose exhaustion [Kriegel et al. (1994) Biochemistry 33, 148-152], while for serine-157 it occurs in vitro with ATP in the presence of nonphosphorylateable five-carbon analogues of glucose [Heidrich et al. (1997) Biochemistry 36, 1960-1964]. We show now by site-directed mutagenesis and sedimentation analysis that serine-14 phosphorylation affects the oligomeric state of hexokinase, its substitution by glutamate causing complete dissociation; glutamate exchange for serine-157 does not. Phosphorylation of wild-type hexokinase at serine-14 likewise causes dissociation in vitro. In view of the higher glucose affinity of monomeric hexokinase and the high hexokinase concentration in yeast [Womack, F., and Colowick, S. P. (1978) Arch. Biochem. Biophys. 191, 742-747; Mayes, E. L., Hoggett, J. G., and Kellett, G. L. (1983) Eur. J. Biochem. 133, 127-134], we speculate that the in vivo phosphorylation at serine-14 as transiently occurring in glucose derepression might provide a mechanism to improve glucose utilization from low level and/or that nuclear localization of the monomer might be involved in the signal transduction whereby glucose causes catabolite repression.

Amino Acid Sequence↗

PubMed1998

Different expression of the alpha2-macroglobulin receptor/low-density lipoprotein receptor-related protein in human keratinocytes and fibroblasts.

We compared, using a combination of different immunological methods and by competitive PCR, the expression of the alpha2-macroglobulin receptor/low-density lipoprotein receptor-related protein (alpha2-M-R/LRP) in human keratinocytes and fibroblasts. This receptor has previously been found in skin only in dermal cells associated with fibroblasts and dendritic cells. For immunodetection we used mouse monoclonal antibodies against the two subunits of the receptor and against the receptor-associated protein (RAP), known as the regulatory protein of the receptor activity. The alpha2-M-R/LRP was found to be predominantly located intracellularly in keratinocytes whereas a distinct labelling of the outer membrane surface was found in fibroblasts. RAP is abundant in fibroblasts but is less expressed in keratinocytes. In frozen skin sections receptor immunoreactivity was detected in the epidermis with increased reactivity of basal keratinocytes, as well as in the dermis in association with dermal fibroblasts. By immunoprecipitation of biotinylated cell extracts, polypeptides were identified corresponding to the alpha-subunit and beta-subunit of the receptor as well as to the coprecipitating RAP. Competitive PCR revealed the presence of 67.9 and 2049.7 ag of alpha2-M-R/LRP mRNA per cell in keratinocytes and fibroblasts, respectively. The results demonstrate that both cell types express alpha-M-R/LRP mRNA and contain receptor protein as well as RAP but in different quantities and subcellular localizations.

Animals↗

PubMed1997

Autophosphorylation-inactivation site of hexokinase 2 in Saccharomyces cerevisiae.

Hexokinase 2 from Saccharomyces cerevisiae is phosphorylated in vivo at serine-15 [Kriegel et al. (1994) Biochemistry 33, 148-152] and undergoes ATP-dependent autophosphorylation-inactivation in vitro when incubated in the presence of D-xylose [Fernandez et al. (1988) J. Gen. Microbiol. 134, 2493-2498]. This study identifies the site of inactivation by autophosphorylation as serine-158 by observation of a single tryptic peptide difference, peptide sequencing, and size determination by mass spectrometry. Mutation of serine-158 to alanine and cysteine, respectively, prevents autophosphorylation and causes a drastic decrease of the catalytic activity while mutational change to glutamate results in a complete loss of enzyme activity. The catalytically active mutant enzymes display an increased affinity for glucose and exhibit higher K(M) with respect to MgATP. Phosphoserine/phosphothreonine-specific protein phosphatase-2A completely reverses the autophosphorylative inactivation of the wild-type enzyme.

Alanine↗