Abstract
Members of the c-Jun NH2-terminal kinase (JNK) family play crucial roles in cell activation, differentiation, and apoptosis. Although many studies have indicated that JNK1 and JNK2 have functional differences and redundancy, the upstream signaling pathway that selectively activates JNK1 or JNK2 remains unknown. In this study, we have revealed a selective mechanism of JNK activation, in which JNK2, but not JNK1, was regulated by CARMA1, a scaffold molecule, after stimulation of the T cell receptor (TCR). This CARMA1-dependent regulation of JNK2 worked through the scaffold molecule Bcl10, which was inducibly associated with JNK2 and served as a JNK-interacting protein (JIP)-like scaffold to assemble the kinases JNK2, MKK7, and TAK1. Finally, we showed that CARMA1- and Bcl10-mediated JNK2 activation had a critical role in regulating the amount of c-Jun protein. Together, our studies provide genetic evidence that JNK1 and JNK2 are differentially regulated in the TCR-signaling pathway and play different functions.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 55-66 |
| Number of pages | 12 |
| Journal | Immunity |
| Volume | 26 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2007 |
| Externally published | Yes |
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Keywords
- MOLIMMUNO
- SIGNALING
ASJC Scopus subject areas
- Immunology and Allergy
- Infectious Diseases
- Immunology
Cite this
The CARMA1-Bcl10 Signaling Complex Selectively Regulates JNK2 Kinase in the T Cell Receptor-Signaling Pathway. / Blonska, Marzenna; Pappu, Bhanu P.; Matsumoto, Reiko; Li, Hongxiu; Su, Bing; Wang, Demin; Lin, Xin.
In: Immunity, Vol. 26, No. 1, 01.2007, p. 55-66.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The CARMA1-Bcl10 Signaling Complex Selectively Regulates JNK2 Kinase in the T Cell Receptor-Signaling Pathway
AU - Blonska, Marzenna
AU - Pappu, Bhanu P.
AU - Matsumoto, Reiko
AU - Li, Hongxiu
AU - Su, Bing
AU - Wang, Demin
AU - Lin, Xin
PY - 2007/1
Y1 - 2007/1
N2 - Members of the c-Jun NH2-terminal kinase (JNK) family play crucial roles in cell activation, differentiation, and apoptosis. Although many studies have indicated that JNK1 and JNK2 have functional differences and redundancy, the upstream signaling pathway that selectively activates JNK1 or JNK2 remains unknown. In this study, we have revealed a selective mechanism of JNK activation, in which JNK2, but not JNK1, was regulated by CARMA1, a scaffold molecule, after stimulation of the T cell receptor (TCR). This CARMA1-dependent regulation of JNK2 worked through the scaffold molecule Bcl10, which was inducibly associated with JNK2 and served as a JNK-interacting protein (JIP)-like scaffold to assemble the kinases JNK2, MKK7, and TAK1. Finally, we showed that CARMA1- and Bcl10-mediated JNK2 activation had a critical role in regulating the amount of c-Jun protein. Together, our studies provide genetic evidence that JNK1 and JNK2 are differentially regulated in the TCR-signaling pathway and play different functions.
AB - Members of the c-Jun NH2-terminal kinase (JNK) family play crucial roles in cell activation, differentiation, and apoptosis. Although many studies have indicated that JNK1 and JNK2 have functional differences and redundancy, the upstream signaling pathway that selectively activates JNK1 or JNK2 remains unknown. In this study, we have revealed a selective mechanism of JNK activation, in which JNK2, but not JNK1, was regulated by CARMA1, a scaffold molecule, after stimulation of the T cell receptor (TCR). This CARMA1-dependent regulation of JNK2 worked through the scaffold molecule Bcl10, which was inducibly associated with JNK2 and served as a JNK-interacting protein (JIP)-like scaffold to assemble the kinases JNK2, MKK7, and TAK1. Finally, we showed that CARMA1- and Bcl10-mediated JNK2 activation had a critical role in regulating the amount of c-Jun protein. Together, our studies provide genetic evidence that JNK1 and JNK2 are differentially regulated in the TCR-signaling pathway and play different functions.
KW - MOLIMMUNO
KW - SIGNALING
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UR - http://www.scopus.com/inward/citedby.url?scp=33846235557&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2006.11.008
DO - 10.1016/j.immuni.2006.11.008
M3 - Article
C2 - 17189706
AN - SCOPUS:33846235557
VL - 26
SP - 55
EP - 66
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 1
ER -