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Molecular and Cellular Biology, October 2001, p. 6939-6950, Vol. 21, No. 20
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.20.6939-6950.2001

Membrane Raft-Dependent Regulation of Phospholipase Cgamma -1 Activation in T Lymphocytes

Maria-Concetta Verí,1 Karen E. DeBell,1 Maria-Cristina Seminario,2 Angela DiBaldassarre,3 Ilona Reischl,4 Rashmi Rawat,1 Laurie Graham,1 Cristiana Noviello,1 Barbara L. Rellahan,1 Sebastiano Miscia,3 Ronald L. Wange,2 and Ezio Bonvini1,*

Laboratory of Immunobiology, Division of Monoclonal Antibodies, Center for Biologics Evaluation & Research,1 and Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health,4 Bethesda, Maryland 20892; Laboratory of Biological Chemistry, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 212242; and Istituto di Morfologia Umana Normale, Università "G. D'Annunzio," 66100 Chieti, Italy3

Received 24 October 2000/Returned for modification 21 December 2000/Accepted 28 June 2001

Numerous signaling molecules associate with lipid rafts, either constitutively or after engagement of surface receptors. One such molecule, phospholipase Cgamma -1 (PLCgamma 1), translocates from the cytosol to lipid rafts during T-cell receptor (TCR) signaling. To investigate the role played by lipid rafts in the activation of this molecule in T cells, an influenza virus hemagglutinin A (HA)-tagged PLCgamma 1 was ectopically expressed in Jurkat T cells and targeted to these microdomains by the addition of a dual-acylation signal. Raft-targeted PLCgamma 1 was constitutively tyrosine phosphorylated and induced constitutive NF-AT-dependent transcription and interleukin-2 secretion in Jurkat cells. Tyrosine phosphorylation of raft-targeted PLCgamma 1 did not require Zap-70 or the interaction with the adapters Lat and Slp-76, molecules that are necessary for TCR signaling. In contrast, the Src family kinase Lck was required. Coexpression in HEK 293T cells of PLCgamma 1-HA with Lck or the Tec family kinase Rlk resulted in preferential phosphorylation of raft-targeted PLCgamma 1 over wild-type PLCgamma 1. These data show that localization of PLCgamma 1 in lipid rafts is sufficient for its activation and demonstrate a role for lipid rafts as microdomains that dynamically segregate and integrate PLCgamma 1 with other signaling components.

* Corresponding author. Mailing address: HFM-564, LIB, DMA, OTRR, CBER, Bldg. 29B, Rm. 3NN10, 29 Lincoln Dr. MSC-4555, Bethesda, MD 20892-4555. Phone: (301) 827-0714. Fax: (301) 827-0852. E-mail: bonvini{at}mail.nih.gov.

Molecular and Cellular Biology, October 2001, p. 6939-6950, Vol. 21, No. 20
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.20.6939-6950.2001


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