Abnormal migration phenotype of mitogen-activated protein kinase-activated protein kinase 2-/- neutrophils in Zigmond chambers containing formyl-methionyl-leucyl-phenylalanine gradients

被引:68
作者
Hannigan, MO
Zhan, LJ
Ai, YX
Kotlyarov, A
Gaestel, M
Huang, CK
机构
[1] Univ Connecticut, Ctr Hlth, Dept Pathol, Farmington, CT 06030 USA
[2] Hannover Med Sch, Inst Biochem, Ctr Biochem, Hannover, Germany
关键词
D O I
10.4049/jimmunol.167.7.3953
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Time-lapsed video microscopy and confocal imaging were used to study the migration of wild-type (WT) and mitogen-activated protein kinase-activated protein kinase 2 (MK2)(-/-) mouse neutrophils in Zigmond chambers containing fMLP gradients. Confocal images of polarized WT neutrophils showed an intracellular gradient of phospho-MK2 from the anterior to the posterior region of the neutrophils. Compared with WT neutrophils, MK2(-/-) neutrophils showed a partial loss of directionality but higher migration speed. Immunoblotting experiments showed a lower protein level of p38 mitogen-activated protein kinase and a loss of fMLP-induced extracellular signal-related kinase phosphorylation in MK2(-/-) neutrophils. These results suggest that MK2 plays an important role in the regulation of neutrophil migration and may also affect other signaling molecules.
引用
收藏
页码:3953 / 3961
页数:9
相关论文
共 78 条
[1]   A role for Cdc42 in macrophage chemotaxis [J].
Allen, WE ;
Zicha, D ;
Ridley, AJ ;
Jones, GE .
JOURNAL OF CELL BIOLOGY, 1998, 141 (05) :1147-1157
[2]   Gelsolin is a downstream effector of rac for fibroblast motility [J].
Azuma, T ;
Witke, W ;
Stossel, TT ;
Hartwig, JH ;
Kwiatkowski, DJ .
EMBO JOURNAL, 1998, 17 (05) :1362-1370
[3]   Ras and Rho GTPases: A family reunion [J].
Bar-Sagi, D ;
Hall, A .
CELL, 2000, 103 (02) :227-238
[4]   Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2 [J].
Ben-Levy, R ;
Hooper, S ;
Wilson, R ;
Paterson, HF ;
Marshall, CJ .
CURRENT BIOLOGY, 1998, 8 (19) :1049-1057
[5]   IDENTIFICATION OF NOVEL PHOSPHORYLATION SITES REQUIRED FOR ACTIVATION OF MAPKAP KINASE-2 [J].
BENLEVY, R ;
LEIGHTON, IA ;
DOZA, YN ;
ATTWOOD, P ;
MORRICE, N ;
MARSHALL, CJ ;
COHEN, P .
EMBO JOURNAL, 1995, 14 (23) :5920-5930
[6]   Chromosomal rearrangements occur in S-cerevisiae rfa1 mutator mutants due to mutagenic lesions processed by double-strand-break repair [J].
Chen, C ;
Umezu, K ;
Kolodner, RD .
MOLECULAR CELL, 1998, 2 (01) :9-22
[7]  
Cohen P, 1996, Adv Pharmacol, V36, P15, DOI 10.1016/S1054-3589(08)60574-8
[8]   Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB [J].
Deak, M ;
Clifton, AD ;
Lucocq, JM ;
Alessi, DR .
EMBO JOURNAL, 1998, 17 (15) :4426-4441
[9]   Inhibition of p38 mitogen activate kinase attenuates the severity of pancreatitis-induced adult respiratory distress syndrome [J].
Denham, W ;
Yang, J ;
Wang, HC ;
Botchkina, G ;
Tracey, KJ ;
Norman, J .
CRITICAL CARE MEDICINE, 2000, 28 (07) :2567-2572
[10]  
Detmers PA, 1998, J IMMUNOL, V161, P1921