Protein phosphatase 2A plays a critical role in interleukin-2-induced beta 2-integrin dependent homotypic adhesion in human CD4+ T cell lines

J Brockdorff; M Nielsen; A Svejgaard; P Dobson; C Röpke; C Geisler; N Odum

doi:10.1006/cyto.1996.0173

Protein phosphatase 2A plays a critical role in interleukin-2-induced beta 2-integrin dependent homotypic adhesion in human CD4+ T cell lines

J Brockdorff, M Nielsen, A Svejgaard, P Dobson, C Röpke, C Geisler, N Odum

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

9 Citationer (Scopus)

Abstract

Udgivelsesdato: 1997-May

Originalsprog	Engelsk
Tidsskrift	Cytokine
Vol/bind	9
Udgave nummer	5
Sider (fra-til)	333-9
Antal sider	6
ISSN	1043-4666
DOI	https://doi.org/10.1006/cyto.1996.0173
Status	Udgivet - 1997

Bibliografisk note

Keywords: Antigens, CD18; CD4-Positive T-Lymphocytes; Cell Adhesion; Cell Line; Cyclins; Humans; Interleukin-2; Okadaic Acid; Phosphoprotein Phosphatases; Protein Phosphatase 2

Adgang til dokumentet

10.1006/cyto.1996.0173

Citationsformater

@article{251af900b0a511ddb538000ea68e967b,

title = "Protein phosphatase 2A plays a critical role in interleukin-2-induced beta 2-integrin dependent homotypic adhesion in human CD4+ T cell lines",

abstract = "Besides its function as a growth factor for T lymphocytes, interleukin 2 (IL-2) induces beta 2-integrin mediated adhesion, migration, and extravasation of T lymphocytes. It is, however, largely unknown how IL-2 receptors (IL-2R) are coupled to the beta 2-integrin adhesion pathway. Because IL-2 modulates enzymatic activity and/or subcellular distribution of serine/threonine phosphatases 1 and 2A (PP1/PP2A) in T cells, we examined the role of these phosphatases in IL-2 induced homotypic adhesion in antigen specific human CD4+ T cell lines. We show that calyculin A, a potent inhibitor of PP1 and PP2A, blocks PP1/PP2A activity and IL-2 induced adhesion, whereas cyclosporin A, an inhibitor of protein serine/threonine phosphatase 2B (PP2B), does not, suggesting that PP1 and/or PP2A are involved in IL-2 induced adhesion. Endothall, which preferentially inhibits PP2A, strongly inhibited cytokine induced adhesion, whereas the structurally related compound 1,4-dimethylendothall had no effect on either phosphatase activity or the adhesion response. Okadaic acid, which preferentially inhibits PP2A, almost completely blocked IL-2-induced adhesion, whereas tautomycin, a potent inhibitor of PP1, had no inhibitory effect on cytokine induced adhesion at concentrations which strongly inhibited phosphatase activity. In conclusion, these data provide evidence that PP2A plays a critical role in IL-2-induced beta 2-integrin-dependent adhesion of human T cell lines.",

author = "J Brockdorff and M Nielsen and A Svejgaard and P Dobson and C R{\"o}pke and C Geisler and N Odum",

note = "Keywords: Antigens, CD18; CD4-Positive T-Lymphocytes; Cell Adhesion; Cell Line; Cyclins; Humans; Interleukin-2; Okadaic Acid; Phosphoprotein Phosphatases; Protein Phosphatase 2",

year = "1997",

doi = "10.1006/cyto.1996.0173",

language = "English",

volume = "9",

pages = "333--9",

journal = "Cytokine",

issn = "1043-4666",

publisher = "Academic Press",

number = "5",

}

TY - JOUR

T1 - Protein phosphatase 2A plays a critical role in interleukin-2-induced beta 2-integrin dependent homotypic adhesion in human CD4+ T cell lines

AU - Brockdorff, J

AU - Nielsen, M

AU - Svejgaard, A

AU - Dobson, P

AU - Röpke, C

AU - Geisler, C

AU - Odum, N

N1 - Keywords: Antigens, CD18; CD4-Positive T-Lymphocytes; Cell Adhesion; Cell Line; Cyclins; Humans; Interleukin-2; Okadaic Acid; Phosphoprotein Phosphatases; Protein Phosphatase 2

PY - 1997

Y1 - 1997

N2 - Besides its function as a growth factor for T lymphocytes, interleukin 2 (IL-2) induces beta 2-integrin mediated adhesion, migration, and extravasation of T lymphocytes. It is, however, largely unknown how IL-2 receptors (IL-2R) are coupled to the beta 2-integrin adhesion pathway. Because IL-2 modulates enzymatic activity and/or subcellular distribution of serine/threonine phosphatases 1 and 2A (PP1/PP2A) in T cells, we examined the role of these phosphatases in IL-2 induced homotypic adhesion in antigen specific human CD4+ T cell lines. We show that calyculin A, a potent inhibitor of PP1 and PP2A, blocks PP1/PP2A activity and IL-2 induced adhesion, whereas cyclosporin A, an inhibitor of protein serine/threonine phosphatase 2B (PP2B), does not, suggesting that PP1 and/or PP2A are involved in IL-2 induced adhesion. Endothall, which preferentially inhibits PP2A, strongly inhibited cytokine induced adhesion, whereas the structurally related compound 1,4-dimethylendothall had no effect on either phosphatase activity or the adhesion response. Okadaic acid, which preferentially inhibits PP2A, almost completely blocked IL-2-induced adhesion, whereas tautomycin, a potent inhibitor of PP1, had no inhibitory effect on cytokine induced adhesion at concentrations which strongly inhibited phosphatase activity. In conclusion, these data provide evidence that PP2A plays a critical role in IL-2-induced beta 2-integrin-dependent adhesion of human T cell lines.

AB - Besides its function as a growth factor for T lymphocytes, interleukin 2 (IL-2) induces beta 2-integrin mediated adhesion, migration, and extravasation of T lymphocytes. It is, however, largely unknown how IL-2 receptors (IL-2R) are coupled to the beta 2-integrin adhesion pathway. Because IL-2 modulates enzymatic activity and/or subcellular distribution of serine/threonine phosphatases 1 and 2A (PP1/PP2A) in T cells, we examined the role of these phosphatases in IL-2 induced homotypic adhesion in antigen specific human CD4+ T cell lines. We show that calyculin A, a potent inhibitor of PP1 and PP2A, blocks PP1/PP2A activity and IL-2 induced adhesion, whereas cyclosporin A, an inhibitor of protein serine/threonine phosphatase 2B (PP2B), does not, suggesting that PP1 and/or PP2A are involved in IL-2 induced adhesion. Endothall, which preferentially inhibits PP2A, strongly inhibited cytokine induced adhesion, whereas the structurally related compound 1,4-dimethylendothall had no effect on either phosphatase activity or the adhesion response. Okadaic acid, which preferentially inhibits PP2A, almost completely blocked IL-2-induced adhesion, whereas tautomycin, a potent inhibitor of PP1, had no inhibitory effect on cytokine induced adhesion at concentrations which strongly inhibited phosphatase activity. In conclusion, these data provide evidence that PP2A plays a critical role in IL-2-induced beta 2-integrin-dependent adhesion of human T cell lines.

U2 - 10.1006/cyto.1996.0173

DO - 10.1006/cyto.1996.0173

M3 - Journal article

C2 - 9195132

SN - 1043-4666

VL - 9

SP - 333

EP - 339

JO - Cytokine

JF - Cytokine

IS - 5

ER -