IgM is the first antibody to be produced in a humoral immune response and plays an important role in the primary stages of immunity. Here we describe a mouse Fc receptor, designated Fc alpha/microR, and its human homolog, that bind both IgM and IgA with intermediate or high affinity. Fc alpha/microR is constitutively expressed on the majority of B lymphocytes and macrophages. Cross-linking Fc alpha/microR expressed on a pro-B cell line Ba/F3 transfectant with soluble IgM or IgM-coated microparticles induced internalization of the receptor. Fc alpha/microR also mediated primary B lymphocyte endocytosis of IgM-coated Staphylococcus aureus. Thus, Fc alpha/microR is involved in the primary stages of the immune response to microbes.

TRPM7/ChaK1 is a unique channel/kinase that contains a TRPM channel domain with 6 transmembrane segments fused to a novel serine-threonine kinase domain at its C terminus. The goal of this study was to investigate a possible role of kinase activity and autophosphorylation in regulation of channel activity of TRPM7/ChaK1. Residues essential for kinase activity were identified by site-directed mutagenesis. Two major sites of autophosphorylation were identified in vitro by mass spectrometry at Ser 1511 and Ser 1567 , and these sites were found to be phosphorylated in intact cells. TRPM7/ ChaK1 is a cation-selective channel that exhibits strong outward rectification and inhibition by millimolar levels of internal [Mg 2؉ ]. Mutation of the two autophosphorylation sites or of a key catalytic site that abolished kinase activity did not alter channel activity measured by whole-cell recording or Ca 2؉ influx. Inhibition by internal Mg 2؉ was also unaffected in the autophosphorylation site or "kinase-dead" mutants. Moreover, kinase activity was enhanced by Mg 2؉ , was decreased by Zn 2؉ , and was unaffected by Ca 2؉ . In contrast, channel activity was inhibited by all three of these divalent cations. However, deletion of much of C-terminal kinase domain resulted in expression of an apparently inactive channel. We conclude that neither current activity nor regulation by internal Mg 2؉ is affected by kinase activity or autophosphorylation but that the kinase domain may play a structural role in channel assembly or subcellular localization.Recent studies have characterized several unique protein kinases that display no amino acid sequence similarity to the superfamily of protein kinase A-related enzymes, including eukaryotic elongation factor-2 kinase (EF2K) 1 and Dictyostelium myosin heavy chain kinases A, B, and C (MHCK A-C). Several additional catalytic domains related to EF2K and MHCK have been identified through data base searches in mammals as well as in nematode worm, although the function of these potential protein kinases is not known (1-3). Using this approach, we and others identified an 1863-amino acid polypeptide (termed ChaK for channel kinase) that contained a TRP-related channel domain fused to the atypical kinase domain at its C terminus (3, 4). The same gene product was also identified in a yeast two-hybrid screen using a portion of phospholipase C ␤1 as bait (and termed TRP-PLIK) (5) and in a screen for TRP-related channels (and termed LTRPC7) (6). Based on revised nomenclature for TRP channels, the kinasecontaining TRP has been termed TRPM7/ChaK1 based on its similarity to long TRP family members, melastatin, MTR1 (TRPM5), and LTRPC2 (TRPM2) (7). A closely related gene, TRPM6/ChaK2 has also been identified as being mutated in familial hypomagnesemia (8, 9), and a key role for both TRPM6 and TRPM7 has been suggested in Mg 2ϩ homeostasis (8 -11).Members of the TRP family of channels contain six predicted transmembrane segments and are related to the superfamily of ion channels that include voltage-gated K ϩ...

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S. aureus cell envelope antigen is a new candidate for the induction of IgA nephropathy.

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