High impact information on ANXA2

• Our results indicate that either calpactin or p36 is essential for exocytosis [1].
• We show here that both calpactin and calpactin heavy chain (p36) reconstitute secretion in permeabilized chromaffin cells in which secretion has been reduced as a result of leakage of cellular components [1].
• These differences suggest that the N-terminal portion of p36 modulates the Ca2+/lipid binding sites in the core portion of p36 (ref.5) [2].
• A synthetic peptide corresponding to the NH2-terminal domain of p36 which contains the phosphorylation sites was microinjected into individual chromaffin cells and catecholamine secretion was monitored by amperometry [3].
• By quantitative confocal immunofluorescence, immunoreplica analysis and immunoprecipitation, we show here the translocation of p36 from the cytosol to a subplasmalemmal Triton X-100 insoluble fraction in chromaffin cells following nicotinic stimulation [3].

Biological context of ANXA2

• It was reported previously that oxidative stress from exogenous hydrogen peroxide or generated in response to tumor necrosis factor-alpha results in the glutathionylation of Cys(8) of annexin A2 [4].
• The 5'- and 3'-ends of p36/6 contained 54 and 307 base pairs of untranslated sequence, respectively [5].
• Annexin II is a member of a multigene family of Ca2+-regulated, membrane-binding proteins implicated through biochemical and perforated cell experiments in Ca2+-triggered secretion [6].
• A region of the p36 subunit of AIIt (Phe306-Ser313) was found to contain a Cardin-Weintraub consensus sequence for glycosaminoglycan recognition [7].
• Mitogenesis, cell migration, and loss of focal adhesions induced by tenascin-C interacting with its cell surface receptor, annexin II [8].

Anatomical context of ANXA2

• Examination of poly(A)+ RNA prepared from the Madin-Darby cell line indicated a p36 mRNA species of about 1.6 kilobases [5].
• We have isolated the p36-p10 complex from bovine intestinal epithelium and analyzed the amino terminus of both subunits [9].
• These data show that annexin II receptors on endothelial cells mediate several cell regulatory functions attributed to tenascin-C, potentially through modulation of intracellular signalling pathways [8].
• A nonapeptide to the putative F-actin binding site of annexin-II tetramer inhibits its calcium-dependent activation of actin filament bundling [10].
• This increase was accompanied by the redistribution of caveolin from a high density to a low density membrane compartment, previously shown to require cholesterol, and increased binding of the annexin II-p11 complex to membranes, consistent with other studies indicating cholesterol-dependent binding of annexin II to membranes [11].

Associations of ANXA2 with chemical compounds

• This peptide blocked completely the nicotine-induced recruitment of p36 to the cell periphery and strongly inhibited exocytosis evoked by either nicotine or high K+ [3].
• Intestinal p36 could be effectively labeled on a single tyrosine in vitro with immunoprecipitated pp60v-src and [gamma-32P]ATP [9].
• We have analyzed its role in the regulation of volume-activated chloride currents (ICl, vol) by loading the cells via the patch pipette with a peptide comprising the N-terminal 14 residues of annexin II [12].
• Characterization of the heparin binding properties of annexin II tetramer [7].
• Within most cells annexin II resides in a tight heterotetrameric complex with a cellular protein ligand, p11, and complex formation is mediated via the N-terminal 14 residues of annexin II including the N-terminal acetyl group [6].

Physical interactions of ANXA2

• Annexin II also cosediments with GF and binds to GFAP, although to much smaller extents [13].
• Finally, we demonstrate that fetuin-A binds to annexin II at the cell membrane of BVSMC [14].

Other interactions of ANXA2

• The annexin A2-S100A10 heterotetramer (AIIt) is a multifunctional Ca(2+)-dependent, phospholipid-binding, and F-actin-binding phosphoprotein composed of two annexin A2 subunits and two S100A10 subunits [4].
• Protein kinase C catalyzes the incorporation of about 1.1, 0.7 and 0.4 mole of phosphate per mole of Lipocortin-I (P35), Lipocortin-II (P36) and Lipocortin-85 (P36 oligomer) respectively [15].
• Four of these proteins were identified by Western blotting or amino acid sequencing as lactoferrin, annexin II, vimentin, and heavy-chain immunoglobulin [16].

Analytical, diagnostic and therapeutic context of ANXA2

• From immunoblotting, the level of p36 in cerebellum was found to decline during development [17].
• The Ca(2+) dissociation constants, as determined by fluorescence titrations, are similar for the complex and p36 (KD approximately 0.5 x 10(-3) M) [18].

References