scholarly journals Mixed lineage kinase-dependent JNK activation is governed by interactions of scaffold protein JIP with MAPK module components

2001 ◽  
Vol 20 (13) ◽  
pp. 3447-3458 ◽  
Author(s):  
D. Nihalani
2012 ◽  
Vol 288 (4) ◽  
pp. 2428-2440 ◽  
Author(s):  
Rohan K. Humphrey ◽  
Shu Mei A. Yu ◽  
Aditi Bellary ◽  
Sumati Gonuguntla ◽  
Myra Yebra ◽  
...  

2007 ◽  
Vol 27 (7) ◽  
pp. 2431-2441 ◽  
Author(s):  
Deepak Nihalani ◽  
Hetty Wong ◽  
Rakesh Verma ◽  
Lawrence B. Holzman

ABSTRACT JIP1 is a mammalian scaffold protein that assembles and participates in regulating the dynamics and activation of components of the mixed-lineage kinase-dependent JNK module. Mechanisms governing JIP1-JNK module regulation remain unclear. JIP1 is a multiply phosphorylated protein; for this reason, it was hypothesized that signaling by unidentified protein kinases or phosphatases might determine module function. We find that Src family kinases directly bind and tyrosine phosphorylate JIP1 under basal conditions in several naturally occurring systems and, by doing so, appear to provide a regulated signal that increases the affinity of JIP1 for DLK and maintains the JIP-JNK module in a catalytically inactive state.


2005 ◽  
Vol 281 (1) ◽  
pp. 303-312 ◽  
Author(s):  
Zhiheng Xu ◽  
Andrew Sproul ◽  
Wenyi Wang ◽  
Nikolay Kukekov ◽  
Lloyd A. Greene

2001 ◽  
Vol 130 (6) ◽  
pp. 773-781 ◽  
Author(s):  
A. Ikeda ◽  
K. Hasegawa ◽  
M. Masaki ◽  
T. Moriguchi ◽  
E. Nishida ◽  
...  

2015 ◽  
Author(s):  
◽  
Cody A. Cunningham

T lymphocytes are critical mediators of the adaptive immune response. T cell receptor (TCR) mediated cJUN NH2-terminal kinase (JNK) activation is required for mounting proper T cell mediated immune responses. However, little is know as to how JNK activation is coupled to the TCR. This dissertation shows that the scaffold protein Plenty of SH3s (POSH) is required for optimal JNK activation and effector function in both CD4+ and CD8+ T cells. Additionally, this work shows that POSH is dispensable for JNK activation and positive and negative selection in developing thymocytes. Thus, POSH couples the TCR to JNK activation in a cell type and developmental stage dependent manner. This work also revels a novel target for the treatment of autoimmune disorders such as Type I Diabetes and Multiple Sclerosis.


MAP Kinase ◽  
2015 ◽  
Vol 4 (1) ◽  
Author(s):  
Miriam Hadad ◽  
Sharon Aviram ◽  
Ilona Darlyuk-Saadon ◽  
Ksenya Cohen-Katsenelson ◽  
Alan J. Whitmarsh ◽  
...  

Mitogen-activated protein kinases (MAPKs) form a kinase tier module in which MAPK, MAP2K and MAP3K are held by scaffold proteins. The scaffold proteins serve as a protein platform for selective and spatial kinase activation. The precise mechanism by which the scaffold proteins function has not yet been fully explained. WD40-repeat protein 62, WDR62 is a novel scaffold protein of the c-Jun N-terminal kinase (JNK) pathway. WDR62 is a 1523 a.a. long protein with no significant sequence homology to a known gene. Previously WDR62 was shown to associate with JNK and MKK4/7 in a modular fashion. Here, we show that WDR62 is able to associate with multiple members of the MAP3K of the mixed lineage kinase family and we map WDR62-MLK3 interacting domains. We identify two separable interacting domains within WDR62 and MLK3 proteins that can cross associate. MLK3 association with WDR62 is independent of JNK and MKK4/7 domains and activities. CDC42 activation disrupts WDR62-MLK3 association independent of MLK3 kinase activity.


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