Sprouty: a controversial role in receptor tyrosine kinase signalling pathways

2003 ◽  
Vol 31 (6) ◽  
pp. 1445-1446 ◽  
Author(s):  
X. Li ◽  
L. Wheldon ◽  
J.K. Heath
Keyword(s):  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Functional Divergence ◽  
Signalling Pathways ◽  
Signalling Molecules ◽  
Rich Domain ◽  
Growth Factor Signalling ◽  
Cysteine Rich Domain ◽  
Growth Factor Signalling Pathway

Sprouty was first identified in Drosophila as a novel antagonist of the fibroblast growth factor signalling pathway. Sprouty proteins comprise a big family, members of which are characterized by a cysteine-rich domain which confers inhibitory activity, whereas differences in the N-terminal region may be responsible for functional divergence. The role of Sprouty in RTK (receptor tyrosine kinase) signalling pathways is still controversial. Sprouty may negatively or positively regulate RTK signalling via differential interaction with different signalling molecules, and hence exert different mechanism of action.

scholarly journals Ror2/Frizzled Complex Mediates Wnt5a-Induced AP-1 Activation by Regulating Dishevelled Polymerization

2010 ◽  
Vol 30 (14) ◽  
pp. 3610-3619 ◽  
Author(s):  
Michiru Nishita ◽  
Sumiyo Itsukushima ◽  
Akira Nomachi ◽  
Mitsuharu Endo ◽  
ZhiChao Wang ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Wnt Pathway ◽  
Receptor Complex ◽  
Jnk Pathway ◽  
Rich Domain ◽  
Canonical Wnt Pathway ◽  
Receptor Component ◽  
Canonical Wnt ◽  
Cysteine Rich Domain

ABSTRACT The receptor tyrosine kinase Ror2 acts as a receptor or coreceptor for Wnt5a to mediate Wnt5a-induced activation of the Wnt/JNK pathway and inhibition of the β-catenin-dependent canonical Wnt pathway. However, little is known about how Ror2 cooperates with another receptor component(s) to mediate Wnt5a signaling. We show here that Ror2 regulates Wnt5a-induced polymerization of Dishevelled (Dvl) and that this Ror2-mediated regulation of Dvl is independent of the cytoplasmic region of Ror2. Ror2 can associate with Frizzled7 (Fz7) via its extracellular cysteine-rich domain to form a receptor complex that is required for the regulation of Dvl and activation of the AP-1 promoter after Wnt5a stimulation. Suppressed expression of Fz7 indeed results in the inhibition of Wnt5a-induced polymerization of Dvl and AP-1 activation. Interestingly, both the DIX and the DEP domains of Dvl are indispensable for Dvl polymerization and subsequent AP-1 activation after Wnt5a stimulation. We further show that polymerized Dvl is colocalized with Rac1 and that suppressed expression of Rac1 inhibits Wnt5a-induced AP-1 activation. Collectively, our results indicate that Ror2/Fz receptor complex plays an important role in the Wnt5a/Rac1/AP-1 pathway by regulating the polymerization of Dvl.

scholarly journals TRIM31 facilitates K27-linked polyubiquitination of SYK to regulate antifungal immunity

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xueer Wang ◽  
Honghai Zhang ◽  
Zhugui Shao ◽  
Wanxin Zhuang ◽  
Chao Sui ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Fungal Pathogen ◽  
Essential Role ◽  
Molecular Mechanisms ◽  
Systemic Infection ◽  
Lectin Receptors ◽  
Innate And Adaptive Immunity ◽  
Cytokines And Chemokines

AbstractSpleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase, which plays an essential role in both innate and adaptive immunity. However, the key molecular mechanisms that regulate SYK activity are poorly understood. Here we identified the E3 ligase TRIM31 as a crucial regulator of SYK activation. We found that TRIM31 interacted with SYK and catalyzed K27-linked polyubiquitination at Lys375 and Lys517 of SYK. This K27-linked polyubiquitination of SYK promoted its plasma membrane translocation and binding with the C-type lectin receptors (CLRs), and also prevented the interaction with the phosphatase SHP-1. Therefore, deficiency of Trim31 in bone marrow-derived dendritic cells (BMDCs) and macrophages (BMDMs) dampened SYK-mediated signaling and inhibited the secretion of proinflammatory cytokines and chemokines against the fungal pathogen Candida albicans infection. Trim31−/− mice were also more sensitive to C. albicans systemic infection than Trim31+/+ mice and exhibited reduced Th1 and Th17 responses. Overall, our study uncovered the pivotal role of TRIM31-mediated K27-linked polyubiquitination on SYK activation and highlighted the significance of TRIM31 in anti-C. albicans immunity.

The role of Ret receptor tyrosine kinase in dopaminergic neuron development

Neuroscience ◽  
2006 ◽  
Vol 142 (2) ◽  
pp. 391-400 ◽  
Author(s):  
L. Li ◽  
Y. Su ◽  
C. Zhao ◽  
H. Zhao ◽  
G. Liu ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Dopaminergic Neuron ◽  
Neuron Development

scholarly journals Oncogenic role of TYRO3 receptor tyrosine kinase in the progression of pancreatic cancer

2020 ◽  
Vol 470 ◽  
pp. 149-160 ◽  
Author(s):  
Masaki Morimoto ◽  
Yosuke Horikoshi ◽  
Kazuhiro Nakaso ◽  
Tatsuyuki Kurashiki ◽  
Yoshinori Kitagawa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase
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