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Target Concepts:
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Query: EC:3.6.1.3 (
ATPase
)
65,361
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Ca
2+
is a universal intracellular signal. The modulation of cytoplasmic Ca
2+
concentration regulates a plethora of cellular processes, such as: synaptic plasticity, neuronal survival, chemotaxis of immune cells, platelet aggregation, vasodilation, and cardiac excitation-contraction coupling. Rap1 GTPases are ubiquitously expressed binary switches that alternate between active and inactive states and are regulated by diverse families of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Active Rap1 couples extracellular stimulation with intracellular signaling through secondary messengers-cyclic adenosine monophosphate (cAMP), Ca
2+
, and diacylglycerol (DAG). Much evidence indicates that Rap1 signaling intersects with Ca
2+
signaling pathways to control the important cellular functions of platelet activation or neuronal plasticity. Rap1 acts as an effector of Ca
2+
signaling when activated by mechanisms involving Ca
2+
and DAG-activated (CalDAG-) GEFs. Conversely, activated by other GEFs, such as cAMP-dependent
GEF
Epac, Rap1 controls cytoplasmic Ca
2+
levels. It does so by regulating the activity of Ca
2+
signaling proteins such as sarcoendoplasmic reticulum Ca
2+
-
ATPase
(SERCA). In this review, we focus on the physiological significance of the links between Rap1 and Ca
2+
signaling and emphasize the molecular interactions that may offer new targets for the therapy of Alzheimer's disease, hypertension, and atherosclerosis, among other diseases.
...
PMID:Integration of Rap1 and Calcium Signaling. 3212 Aug 17
Microtubules display dynamic turnover during cell migration, leading to cell contractility and focal adhesion maturation regulated by Rho guanosine
triphosphatase
activity. This interplay between microtubules and actomyosin is mediated by
guanine nucleotide exchange factor
(
GEF
)-H1 released after microtubule depolymerization or microtubule disconnection from focal adhesions. However, how GEF-H1 activates Rho upon microtubule disassembly remains elusive. Here, we found that BNIP-2, a BCH domain-containing protein that binds both RhoA and GEF-H1 and traffics with kinesin-1 on microtubules, is important for GEF-H1-driven RhoA activation upon microtubule disassembly. Depletion of BNIP-2 in MDA-MB-231 breast cancer cells decreases RhoA activity and promotes cell migration. Upon nocodazole-induced microtubule disassembly, the interaction between BNIP-2 and GEF-H1 increases, while knockdown of BNIP-2 reduces RhoA activation and cell rounding via uncoupling RhoA-GEF-H1 interaction. Together, these findings revealed that BNIP-2 couples microtubules and focal adhesions via scaffolding GEF-H1 and RhoA, fine-tuning RhoA activity and cell migration.
...
PMID:BNIP-2 retards breast cancer cell migration by coupling microtubule-mediated GEF-H1 and RhoA activation. 3278 68
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