Phosphorylation of a chromaffin granule-binding protein by protein kinase C.

Summers, Theresa A.; Creutz, Carl E.

doi:10.1016/s0021-9258(18)89573-4

Cited by 69 publications

(15 citation statements)

References 31 publications

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“…This notion was further bolstered by demonstrations that PKC could regulate granule exocytosis in other secretory cell types (e.g., mast calls, chromaffin cells, etc.) and could phosphorylate granule-associated proteins (42)(43)(44)(45). To determine whether FcR-or TCK-initiated granule release is, in fact, mediated via a PKC-dependent pathway, one would like to assess the effects of selective and potent PKC inhibitors on this process.…”

Section: Discussionmentioning

confidence: 99%

Fc receptor stimulation of phosphatidylinositol 3-kinase in natural killer cells is associated with protein kinase C-independent granule release and cell-mediated cytotoxicity.

Bonnema

Karnitz

Schoon

et al. 1994

The Journal of Experimental Medicine

130

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Although diverse signaling events are initiated by stimulation of multichain immune recognition receptors on lymphocytes, it remains unclear as to which specific signal transduction pathways are functionally linked to granule exocytosis and cellular cytotoxicity. In the case of natural killer (NK) cells, it has been presumed that the rapid activation of protein kinase C (PKC) enables them to mediate antibody-dependent cellular cytotoxicity (ADCC) and "natural" cytotoxicity toward tumor cells. However, using cloned human NK cells, we determined here that Fc receptor stimulation triggers granule release and ADCC through a PKC-independent pathway. Specifically, pretreatment of NK cells with the selective PKC inhibitor, GF109203X (using concentrations that fully blocked phorbol myristate acetate/ionomycin-induced secretion) had no effect on FcR-initiated granule release or ADCC. In contrast, FcR ligation led to the rapid activation of phosphatidylinositol 3-kinase (PI 3-kinase), and inhibition of this enzyme with the selective inhibitor, wortmannin, blocked FcR-induced granule release and ADCC. Additional experiments showed that, whereas FcR-initiated killing was wortmannin sensitive and GF109203X insensitive, natural cytotoxic activity toward the tumor cell line K562 was wortmannin insensitive and GF109203X sensitive. Taken together, these results suggest that: (a) PI 3-kinase activation induced by FcR ligation is functionally coupled to granule exocytosis and ADCC; and (b) the signaling pathways involved in ADCC vs natural cytotoxicity are distinct.

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Section: Discussionmentioning

confidence: 99%

Fc receptor stimulation of phosphatidylinositol 3-kinase in natural killer cells is associated with protein kinase C-independent granule release and cell-mediated cytotoxicity.

Bonnema

Karnitz

Schoon

et al. 1994

The Journal of Experimental Medicine

130

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“…Annexin I serves as a good substrate for protein kinase C in vitro (Summers & Creutz, 1985). Schlaepfer and Haigler (1988) have shown that human annexin I is phosphorylated in vitro to equal extents on Thr-24, Ser-27, and Ser-28 by protein kinase C. However, these phosphorylation sites are not entirely conserved among different species (Varticovski et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

“…These proteins possess a similar core domain with four or eight conserved 70 amino acid repeats and an amino-terminal domain which varies in length and sequence among different members. Annexin I is a substrate for protein kinase C (PKC)1 (Micheneretal., 1986;Summers & Creutz, 1985) and for the epidermal growth factor receptor kinase Sawyer & Cohen, 1985) both in vitro and in vivo. The sites phosphorylated by these kinases in vitro have been localized to the N-terminal domain (Schlaepfer & Haigler, 1988;Varticovskietal., 1988).…”

mentioning

confidence: 99%

Role of the amino-terminal domain in regulating interactions of annexin I with membranes: Effects of amino-terminal truncation and mutagenesis of the phosphorylation sites

Wang¹,

Creutz²

1994

Biochemistry

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Phosphorylation of the N-terminal tail by protein kinase C strongly inhibits the ability of bovine or human annexin I to aggregate chromaffin granules by increasing the calcium requirement 4-fold (Wang, W., & Creutz, C. E. (1992) Biochemistry 31, 9934-9936). In the present study three forms of human annexin I truncated in the amino terminus at residue Trp-12, Lys-26, or Lys-29 exhibit dramatic differences in their sensitivities to calcium in a chromaffin granule aggregation assay, while the [Ca2+](1/2)max values for binding of the truncated proteins to granule membranes are similar. Cleavage at Trp-12 causes a 3-fold decrease in calcium sensitivity in the membrane aggregation assay, while cleavage at Lys-26 causes a 4-fold enhancement of calcium sensitivity. In contrast, cleavage at Lys-29 results in virtually no change in calcium sensitivity. Mutagenic substitution with negatively charged amino acids of Ser-27, a site for phosphorylation by protein kinase C, or Tyr-21, a site for phosphorylation by the epidermal growth factor receptor kinase, mimics the inhibition of granule-aggregating activity seen with phosphorylation by protein kinase C. When bovine chromaffin cells are stimulated to secrete by nicotine, annexin I is phosphorylated in the amino terminus. Thr-24 and Ser-28, which are sites for phosphorylation by protein kinase C in vitro, are two of the sites phosphorylated in vivo in stimulated chromaffin cells. These data demonstrate that the ability of annexin I to promote membrane aggregation is highly sensitive to changes in the structure of the N-terminal domain of the protein.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Together these data provide a precedent that additional annexins may be capable of forming stable protein-protein interactions. Annexin I and II also exhibit enzyme-substrate interactions in that they can be phosphorylated at their N-termini on serine residues by protein kinase C (PKC) 1 (Summers & Creutz, 1985;Khanna, 1986) and on tyrosine residues by EGF and IGF receptor kinases (annexin I) (Fava & Cohen, 1984;Karasik et al, 1988) and src kinase (annexin II) (Glenney, 1985;Glenney & Tack, 1985), respectively. The binding of proteins to members of the annexin family may play a role in the in ViVo regulation of the annexins.…”

mentioning

confidence: 99%

Calcium-Dependent Binding of the Plasma Protein Apolipoprotein A-I to Two Members of the Annexin Family

Brownawell

Creutz

1996

Biochemistry

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Affinity chromatography with purified annexins coupled to CNBr-activated Sepharose 4B was used to determine the capacity of proteins found in cytosolic fractions of the bovine adrenal medulla to bind to an immobilized annexin in a Ca2+-dependent manner. Several proteins were eluted from a recombinant annexin I column in the presence of 2 mM EGTA, including protein kinase C (PKC), members of the annexin family, and a 26 kDa protein that appeared as the most prominent band on SDS-PAGE. The identities of PKC, annexin I, annexin IV, annexin VI, and annexin VII were confirmed by Western blotting. The 26 kDa protein was purified by anion exchange chromatography on a Poros Q column and determined to be apolipoprotein A-I (apoA-I) by peptide sequencing. Comigration of apoA-I and chromobindin 2 on two-dimensional gels identified apoA-I as chromobindin 2. Overlay assays were performed to verify the apoA-I-annexin I interaction using apoA-I immobilized on nitrocellulose and annexin I in solution with binding detected using anti-annexin I antiserum. Additionally, the ability of biotin-labeled apoA-I in solution to bind to several purified annexins immobilized on nitrocellulose was determined by detection with horseradish peroxidase-conjugated avidin. Using these methods, it was shown that both annexin I and annexin VII bind to bovine apoA-I in a Ca2+-dependent manner. Other annexins, such as annexin IV and annexin VI, do not exhibit this binding. The results suggest that certain annexins may function as extracellular binding sites for plasma proteins.

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Phosphorylation of a chromaffin granule-binding protein by protein kinase C.

Cited by 69 publications

References 31 publications

Fc receptor stimulation of phosphatidylinositol 3-kinase in natural killer cells is associated with protein kinase C-independent granule release and cell-mediated cytotoxicity.

Fc receptor stimulation of phosphatidylinositol 3-kinase in natural killer cells is associated with protein kinase C-independent granule release and cell-mediated cytotoxicity.

Role of the amino-terminal domain in regulating interactions of annexin I with membranes: Effects of amino-terminal truncation and mutagenesis of the phosphorylation sites

Calcium-Dependent Binding of the Plasma Protein Apolipoprotein A-I to Two Members of the Annexin Family

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