Development of a Rapid Approach to Identification of Tyrosine Phosphorylation Sites: Application to PKCδ Phosphorylated upon Activation of the High Affinity Receptor for IgE in Rat Basophilic Leukemia Cells

Szállási, Zoltán; Denning, M. F.; Chang, En-Yuh; Rivera, Juan; Yuspa, Stuart H.; Lehel, Csaba; Oláh, Zoltán; Anderson, W. B.; Blumberg, Peter M.

doi:10.1006/bbrc.1995.2370

Cited by 72 publications

(73 citation statements)

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“…Another possibility is that the function of the regulatory domain is altered by phosphorylation. This is supported by data suggesting that several of the protein kinase C isozymes can become phosphorylated (27,31) and that tyrosine phosphorylation of protein kinase C-␦ occurs on the regulatory domain (43). However, we failed to detect any differences between adherent and suspended cells in the tyrosine phosphorylation of any of the protein kinase C isozymes.…”

Section: Discussionsupporting

confidence: 78%

Differential Effects of the Protein Kinase C Activator Phorbol 12-Myristate 13-Acetate on Calcium Responses and Secretion in Adherent and Suspended RBL-2H3 Mucosal Mast Cells

Wolfe

Chang

Rivera

et al. 1996

Journal of Biological Chemistry

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Adhesion of RBL-2H3 mucosal mast cells to fibronectin-coated surfaces has been linked to changes in secretion and tyrosine kinase activity. We now show that adhesion affects the sensitivity of RBL cells to the protein kinase C activator phorbol 12-myristate 13-acetate (PMA). In suspended cells, PMA inhibited antigen-induced calcium influx (as measured by manganese influx) and changes in intracellular free calcium and had complex effects on antigen-stimulated secretion. However, in adherent cells PMA had little effect on these responses. Suspended cells only secreted in response to thapsigargin if they were co-treated with PMA, while adherent cells secreted in response to thapsigargin alone. The thapsigargin-induced secretion in adherent cells was inhibited by protein kinase C down-regulation and by the protein kinase C inhibitor GF 109203X, but not by calphostin C. We suggest that protein kinase C is constitutively activated in adherent cells, possibly due to modification of the regulatory domain of the enzyme.

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Section: Discussionsupporting

confidence: 78%

Differential Effects of the Protein Kinase C Activator Phorbol 12-Myristate 13-Acetate on Calcium Responses and Secretion in Adherent and Suspended RBL-2H3 Mucosal Mast Cells

Wolfe

Chang

Rivera

et al. 1996

Journal of Biological Chemistry

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“…For example, antigen activation of the immunoglobulin E receptor and consequently tyrosine-phosphorylated PKC d exhibited decreased activity towards the IgE receptor g chain peptide but not towards histone or myelin basic protein peptide (Haleem-Smith et al, 1995). The sites of tyrosine phosphorylation on PKC d may also dier and may contribute to distinct eects of PKC d on substrates (Li et al, 1996;Szallasi et al, 1995).…”

Section: Resultsmentioning

confidence: 99%

Association of PKC δ and active Src in PMA-treated MCF-7 human breast cancer cells

et al. 1998

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“…Tyrosine residues 52 and 187 in the regulatory domain of PKC␦ have been shown to be phosphorylated upon cellular stimulation (42,43). PKC␦ was also found to be phosphorylated on multiple tyrosine residues in the catalytic domain, and phosphorylation of Tyr-512 and -523 was demonstrated to be critical for the activation of PKC␦ by H 2 O 2 (40).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Protein Kinase Cθ Function during T Cell Activation by Lck-mediated Tyrosine Phosphorylation

Liu

Witte

Liu

et al. 2000

Journal of Biological Chemistry

114

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Protein kinase C (PKC) is a novel Ca2؉ -independent PKC isoform, which is selectively expressed in skeletal muscle and hematopoietic cells, especially T cells. In T cells, it colocalizes with the T cell antigen receptor (TCR)⅐CD3 complex in antigen-stimulated T cells and is involved in the transcriptional activation of the interleukin-2 gene. In the present study, we report that PKC is tyrosine phosphorylated in Jurkat T cells upon TCR⅐CD3 activation. The Src family protein-tyrosine kinase, Lck, was critical in TCR-induced tyrosine phosphorylation of PKC. Lck phosphorylated and was associated with the regulatory domain of PKC both in vitro and in intact cells. This association was constitutive, but it was enhanced by T cell activation, with both Srchomology 2 and Src-homology 3 domains of Lck contributing to it. Tyrosine 90 (Tyr-90) in the regulatory domain of PKC was identified as the major phosphorylation site by Lck. A constitutively active mutant of PKC (A148E) could enhance proliferation of Jurkat T cells and synergized with ionomycin to induce nuclear factor of T cells activity. However, mutation of Tyr-90 into phenylalanine markedly reduced (or abolished) these activities. These results suggest that Lck plays an important role in tyrosine phosphorylation of PKC, which may in turn modulate the physiological functions of PKC during TCR-induced T cell activation. Protein kinase C (PKC)1 is a family of serine/threonine kinases that play critical roles in the regulation of differentiation and proliferation in many cell types and in the response to diverse stimuli (reviewed in Refs. 1 and 2). Products of the 10 known mammalian PKC genes are classified into four subfamilies of Ca 2ϩ -dependent (or conventional, PKC␣, -␤, and -␥), Ca 2ϩ -independent (or novel, PKC␦, -⑀, -, and -), atypical (PKC and /), and PKC/D enzymes. Activity of PKC enzymes is regulated by phosphorylation and binding of defined cofactors. Enzyme activation is associated with its redistribution among different cellular compartments, commonly from the cytosolic to the particulate (membrane) fraction. Studies indicate that PKC is also important during T cell activation. This is indicated by the ability of physiological T cell receptor (TCR) ligands to activate PKC and induce its translocation from the cytosol to the particulate fraction; by the ability of PKC inhibitors, or PKC depletion by prolonged phorbol ester treatment, to block lymphocyte signaling and activation; by the requirement for persistent PKC activation during mitogenic T cell activation; and, finally, by the diminished TCR⅐CD3-mediated proliferation in PKC-deficient T cells (reviewed in Ref. 3).PKC is a novel Ca 2ϩ

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Development of a Rapid Approach to Identification of Tyrosine Phosphorylation Sites: Application to PKCδ Phosphorylated upon Activation of the High Affinity Receptor for IgE in Rat Basophilic Leukemia Cells

Cited by 72 publications

References 0 publications

Differential Effects of the Protein Kinase C Activator Phorbol 12-Myristate 13-Acetate on Calcium Responses and Secretion in Adherent and Suspended RBL-2H3 Mucosal Mast Cells

Differential Effects of the Protein Kinase C Activator Phorbol 12-Myristate 13-Acetate on Calcium Responses and Secretion in Adherent and Suspended RBL-2H3 Mucosal Mast Cells

Association of PKC δ and active Src in PMA-treated MCF-7 human breast cancer cells

Regulation of Protein Kinase Cθ Function during T Cell Activation by Lck-mediated Tyrosine Phosphorylation

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