IQGAP1 regulates cytoskeletal dynamics through interactions with the Rho family GTPases Rac1 and Cdc42, F-actin, and beta-catenin. Calmodulin interaction with IQ motifs of IQGAP1 negatively influences these IQGAP1 interactions. Although, calmodulin interacts with IQGAP1 in the absence of Ca(2+) and was suggested to exhibit reduced binding when Ca(2+) bound, recent reports show substantially greater binding when Ca(2+) is present. Binding evaluations have primarily relied on IQGAP1 interaction with calmodulin conjugated to Sepharose 4B. In this study we evaluated the Ca(2+)-dependence of calmodulin interaction with native IQGAP1 using a series of independent biochemical approaches. We found the apparent binding of calmodulin to IQGAP1 was Ca(2+)-independent, being between 5- and 20-fold greater in the absence than in the presence of Ca(2+). In addition, calmodulin interaction with IQGAP1 was negatively regulated by buffer [Ca(2+)] (IC(50)=3.4x10(-7)M). Regulation was specific to Ca(2+), as Ba(2+) was approximately 400-fold less effective than Ca(2+) at modulating the interaction. Moreover, testing of calmodulin mutants demonstrated that apocalmodulin tightly binds IQGAP1 and that the N- and C-terminal pair of EF hands are important for Ca(2+) sensitivity. These data indicate that calmodulin may disassemble from IQGAP1 to facilitate IQGAP1 interaction with effectors of cytoskeletal reorganization during conditions of cell activation that promote increased cytosolic [Ca(2+)].
"IQGAP1 contains multiple protein-interacting domains: the CH (calponin homology) domain binds to F-actin, the WW domain binds to ERK2, the IQ repeat motifs bind to calmodulin and myosin light chain, and the Ras GAP-like domain binds to Cdc42 and Rac1 –. IQGAP1 is also known to bind to E-cadherin and ß-catenin, and is involved in cytoskeltal reorganization and cell adhesion , . On the other hand, IQGAP1 stimulates ß-catenin-mediated transcriptional activation34. "
[Show abstract][Hide abstract] ABSTRACT: Dishevelled (DVL) is a central factor in the Wnt signaling pathway, which is highly conserved among various organisms. DVL plays important roles in transcriptional activation in the nucleus, but the molecular mechanisms underlying their nuclear localization remain unclear. In the present study, we identified IQGAP1 as a regulator of DVL function. In Xenopus embryos, depletion of IQGAP1 reduced Wnt-induced nuclear accumulation of DVL, and expression of Wnt target genes during early embryogenesis. The domains in DVL and IQGAP1 that mediated their interaction are also required for their nuclear localization. Endogenous expression of Wnt target genes was reduced by depletion of IQGAP1 during early embryogenesis, but notably not by depletion of other IQGAP family genes. Moreover, expression of Wnt target genes caused by depletion of endogenous IQGAP1 could be rescued by expression of wild-type IQGAP1, but not IQGAP1 deleting DVL binding region. These results provide the first evidence that IQGAP1 functions as a modulator in the canonical Wnt signaling pathway.
PLoS ONE 04/2013; 8(4):e60865. DOI:10.1371/journal.pone.0060865 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Real-world pattern classification problems usually involve many
attributes. In such a pattern classification problem, all attributes are
not always necessary for the classification task. That is, when we
design a pattern classification system, some attributes may be removable
with no deterioration of its performance. The main aim of this paper is
to describe how the number of attributes can be reduced when we design a
fuzzy rule-based classification system. We use a simple stepwise input
selection mechanism: first the most important two attributes are
selected by the examination of all combinations, then the next best
attribute is added sequentially. By computer simulations on well-known
real-world test problems with many continuous attributes, the
performance of the fuzzy rule-based classification system designed by
the input selection mechanism is examined. Simulation results clearly
show that a small number of selected attributes have high classification
ability for many real-world test problems
Fuzzy Systems, 1997., Proceedings of the Sixth IEEE International Conference on; 08/1997
[Show abstract][Hide abstract] ABSTRACT: The Ras superfamily of small GTPases constitutes a large group of structurally and functionally related proteins. They function as signalling switches in numerous signalling cascades in the cell. During the recent years, an increased awareness of a communication between signalling systems employing Ras-like GTPases and signalling systems employing calcium has emerged. For instance, the intensity of the activation of Ras-like GTPases is regulated by calcium-dependent mechanisms, acting on proteins that facilitate the activation or inactivation of the small GTPases. Other Ras-like GTPases have a direct influence on calcium signalling by regulating the activity of certain calcium channels. In addition, several small GTPases collaborate with calcium signalling in regulating cellular processes, such as cell adhesion, cell migration and exocytosis.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.