Abnormal pattern of tyrosine phosphorylation in unstimulated peripheral blood T lymphocytes from patients with systemic lupus erythematosus

被引:12
作者
Blasini, AM [1 ]
Alonzo, E [1 ]
Chacón, R [1 ]
Riera, R [1 ]
Stekman, IL [1 ]
Rodriguez, MA [1 ]
机构
[1] Hosp Univ Caracas, Ctr Nacl Enfermedades Reumat, Caracas, Venezuela
关键词
SLE; T cells; PTKs; phosphatase activity; CD3;
D O I
10.1191/096120398678920604
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Previous reports have shown abnormal responses mediated via the TCR/CD3 pathway in T lymphocytes from systemic lupus erythematosus (SLE) patients. Recently, we and others have reported augmented TCR/CD3-mediated responses-in lupus T cells. It is possible that the pattern of downstream biochemical signals triggered by TCR/CD3 ligation may be altered in T lymphocytes from patients with SLE, thus leading to abnormal distal cell responses. In this paper we have examined the phosphorylation of proteins on tyrosine residues in peripheral blood T lymphocytes from a group of SLE patients and controls. We found a lower frequency of constitutively tyrosine-phosphorylated 119- and 113-kDa substrates and an enhanced frequency of tyrosine-phosphorylated 66- and 25-kDa proteins in unstimulated cultures of SLE T lymphocytes, suggesting an altered pattern of tyrosine phosphorylation in T cells from patients in vivo. Additionally, the protein tyrosine phosphatase (PTP) activity of CD45 immunoprecipitates was lower in unstimulated lupus T cells and was enhanced after stimulation via the CD3 pathway in lupus but not control T lymphocytes. The present results seem to suggest abnormal regulation of in-vivo tyrosine phosphorylation in T cells from patients with SLE.
引用
收藏
页码:515 / 523
页数:9
相关论文
共 23 条
[1]   ENHANCEMENT OF T-CELL RESPONSIVENESS BY THE LYMPHOCYTE-SPECIFIC TYROSINE PROTEIN-KINASE P56LCK [J].
ABRAHAM, N ;
MICELI, MC ;
PARNES, JR ;
VEILLETTE, A .
NATURE, 1991, 350 (6313) :62-66
[2]   T-LYMPHOCYTES FROM PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS SHOW INCREASED RESPONSE TO INTERLEUKIN-2 AFTER COSTIMULATION WITH OKT3 MONOCLONAL-ANTIBODY AND PHORBOL ESTERS [J].
BLASINI, AM ;
STEKMAN, IL ;
GONZALEZ, F ;
TOSITTI, ML ;
RODRIGUEZ, MA .
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, 1994, 70 (01) :66-72
[3]   REGULATION OF T-CELL RECEPTOR SIGNALING BY A SRC FAMILY PROTEIN-TYROSINE KINASE (P59FYN) [J].
COOKE, MP ;
ABRAHAM, KM ;
FORBUSH, KA ;
PERLMUTTER, RM .
CELL, 1991, 65 (02) :281-291
[4]   DIFFERENTIAL REGULATION OF T-CELL ANTIGEN RESPONSIVENESS BY ISOFORMS OF THE SRC-RELATED TYROSINE PROTEIN-KINASE P59FYN [J].
DAVIDSON, D ;
CHOW, LML ;
FOURNEL, M ;
VEILLETTE, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1992, 175 (06) :1483-1492
[5]   The T cell enigma in lupus [J].
Dayal, AK ;
Kammer, GM .
ARTHRITIS AND RHEUMATISM, 1996, 39 (01) :23-33
[6]   SIGNALING PATHWAYS ACTIVATED BY PROTEIN-TYROSINE PHOSPHORYLATION IN LYMPHOCYTES [J].
DEFRANCO, AL .
CURRENT OPINION IN IMMUNOLOGY, 1994, 6 (03) :364-371
[7]  
HAWKER G, 1993, J RHEUMATOL, V20, P657
[8]   TYROSINE PHOSPHORYLATION OF A C-SRC-LIKE PROTEIN IS INCREASED IN MEMBRANES OF CD4- CD8- LYMPHOCYTES-T FROM LPR/LPR MICE [J].
KATAGIRI, T ;
TING, JPY ;
DY, R ;
PROKOP, C ;
COHEN, P ;
EARP, HS .
MOLECULAR AND CELLULAR BIOLOGY, 1989, 9 (11) :4914-4922
[9]   Altered pattern of TCR/CD3-mediated protein-tyrosyl phosphorylation in T cells from patients with systemic lupus erythematosus - Deficient expression of the T cell receptor zeta chain [J].
Liossis, SNC ;
Ding, XZ ;
Dennis, GJ ;
Tsokos, GC .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (07) :1448-1457
[10]   Lack of SHPTP1 results in src-family kinase hyperactivation and thymocyte hyperresponsiveness [J].
Lorenz, U ;
Ravichandran, KS ;
Burakoff, SJ ;
Neel, BG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (18) :9624-9629