Calpain cleavage of the B isoform of Ins(1,4,5)P3 3-kinase separates the catalytic domain from the membrane anchoring domain
| Autor: | K Pattni, George Banting, Thomas H. Millard |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
inorganic chemicals
Vesicle-associated membrane protein 8 Recombinant Fusion Proteins Green Fluorescent Proteins Molecular Sequence Data Biochemistry Cell membrane chemistry.chemical_compound Cytosol Catalytic Domain medicine Animals Humans Inositol Amino Acid Sequence Molecular Biology Binding Sites biology Calpain Endoplasmic reticulum Cell Membrane Membrane Proteins Cell Biology Rats Cell biology Isoenzymes Luminescent Proteins Phosphotransferases (Alcohol Group Acceptor) medicine.anatomical_structure Microscopy Fluorescence chemistry Membrane protein Protein kinase domain Second messenger system biology.protein HeLa Cells Research Article |
| Zdroj: | Biochemical Journal. 375:643-651 |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/bj20030505 |
| Popis: | Inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3] is one of the key intracellular second messengers in cells and mobilizes Ca2+ stores in the ER (endoplasmic reticulum). Ins(1,4,5)P3 has a short half-life within the cell, and is rapidly metabolized through one of two pathways, one of which involves further phosphorylation of the inositol ring: Ins(1,4,5)P3 3-kinase (IP3-3K) phosphorylates Ins(1,4,5)P3, resulting in the formation of inositol (1,3,4,5)-tetrakisphosphate [Ins(1,3,4,5)P4]. There are three known isoforms of IP3-3K, designated IP3-3KA, IP3-3KB and IP3-3KC. These have differing N-termini, but highly conserved C-termini harbouring the catalytic domain. The three IP3-3K isoforms have different subcellular locations and the B-kinase is uniquely present in both cytosolic and membrane-bound pools. As it is the N-terminus of the B-kinase that differs most from the A- and C-kinases, we have hypothesized that this portion of the protein may be responsible for membrane localization. Although there are no known membrane-targeting protein motifs within the sequence of IP3-3KB, it is found to be tightly associated with the ER membrane. Here, we show that specific regions of the N-terminus of IP3-3KB are necessary and sufficient for efficient membrane localization of the protein. We also report that, in the presence of Ca2+, the kinase domain of IP3-3KB is cleaved from the membrane-anchoring region by calpain. |
| Databáze: | OpenAIRE |
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