Essential role of CIB1 in regulating PAK1 activation and cell migration

Leisner, Tina M.; Liu, Mingjuan; Jaffer, Zahara M.; Chernoff, Jonathan; Parise, Leslie V.

doi:10.1083/jcb.200502090

Cited by 79 publications

(103 citation statements)

References 52 publications

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“…Ca 2ϩ induces a conformational change in CIB1 (17) and modulates the binding and regulatory actions of CIB1 on several CIB1-interacting proteins (18,30). In the present study, the binding of CIB1 to ASK1 was blocked either by ionomycin (Fig.…”

Section: Discussionsupporting

confidence: 48%

CIB1 functions as a Ca ²⁺ -sensitive modulator of stress-induced signaling by targeting ASK1

Yoon¹,

Cho²,

Lee³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Calcium and integrin binding protein 1 (CIB1) is a Ca 2+ -binding protein of 22 kDa that was initially identified as a protein that interacts with integrin α IIb . Although it interacts with various proteins and has been implicated in diverse cellular functions, the molecular mechanism by which CIB1 regulates intracellular signaling networks has remained unclear. We now show that, by targeting apoptosis signal-regulating kinase 1 (ASK1), CIB1 negatively regulates stress-activated MAPK signaling pathways. CIB1 was thus shown to bind to ASK1, to interfere with the recruitment of TRAF2 to ASK1, and to inhibit the autophosphorylation of ASK1 on threonine-838, thereby blocking ASK1 activation. Furthermore, CIB1 mitigated apoptotic cell death initiated either by TNF-α in breast cancer MCF7 cells or by 6-hydroxydopamine (6-OHDA) in dopaminergic cells. Ca 2+ influx induced by membrane depolarization reversed the inhibitory effect of CIB1 on 6-OHDA-induced ASK1 activation and cell death in dopaminergic neurons. These observations thus suggest that CIB1 functions as a Ca 2+ -sensitive negative regulator of ASK1-mediated signaling events.

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Section: Discussionsupporting

confidence: 48%

CIB1 functions as a Ca ²⁺ -sensitive modulator of stress-induced signaling by targeting ASK1

Yoon¹,

Cho²,

Lee³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…Likewise, RhoA activation reduces lamellipodia number in stromal cells (Jaganathan et al, 2007) and leucocytes (Worthylake and Burridge, 2003), but increases it in epithelial cells (Danen et al, 2005). p21-activated kinase-1 (Pak1) prompts migration in several cell lines (Alahari et al, 2004;Kiosses et al 1999), but blocks it in embryo fibroblasts (Leisner et al 2005). Similarly, myosin II inhibition promotes migration of fibrosarcoma cells (Niggli et al, 2006), but diminishes that of endothelial cells, macrophages, and smooth muscle cells (Nakayama et al, 2005).…”

Section: Context-dependent and Paradoxical Functionsmentioning

confidence: 99%

Control of gastrula cell motility by the Goosecoid/Mix.1/ Siamois network: Basic patterns and paradoxical effects

Luu

Nagel

Wacker

et al. 2008

Developmental Dynamics

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In the vegetal half of the Xenopus gastrula, cell populations differ with respect to migration on fibronectin substratum. We show that the paired-class homeodomain transcription factors Goosecoid (Gsc), Mix.1, and Siamois (Sia) are involved in the modulation of migration velocity and cell polarity. Mix.1 is expressed in the whole vegetal half and serves as a competence factor that is necessary, but not sufficient, for rapid cell migration and polarization.

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“…CIB1 is a ubiquitous 191-residue (22 kDa) protein with several functions in cell signaling (2,3). CIB1 has been reported to interact with a number of protein targets, including the platelet integrin ␣IIb subunit (4), sphingosine kinase 1 (5), p21-activated kinase (6), apoptosis signal-regulating kinase (7), polo-like protein kinases (8), and a recently reported new target in the regulation of cardiac hypertrophy, calcineurin B (9). The interaction of CIB1 with the integrin ␣IIb subunit has been studied extensively (10 -13).…”

mentioning

confidence: 99%

Solution Structures of Ca2+-CIB1 and Mg2+-CIB1 and Their Interactions with the Platelet Integrin αIIb Cytoplasmic Domain

Huang

Ishida

Yamniuk

et al. 2011

Journal of Biological Chemistry

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The calcium-and integrin-binding protein 1 (CIB1) is a ubiquitous Ca 2؉ -binding protein and a specific binding partner for the platelet integrin ␣IIb cytoplasmic domain, which confers the key role of CIB1 in hemostasis. CIB1 is also known to be involved in apoptosis, embryogenesis, and the DNA damage response. In this study, the solution structures of both Ca 2؉ -CIB1 and Mg 2؉ -CIB1 were determined using solution-state NMR spectroscopy. The methyl groups of Ile, Leu, and Val were selectively protonated to compensate for the loss of protons due to deuteration. The solution structure of Ca 2؉ -CIB1 possesses smaller opened EF-hands in its C-domain compared with available crystal structures. Ca 2؉ -CIB1 and Mg 2؉ -CIB1 have similar structures, but the N-lobe of Mg 2؉ -CIB1 is slightly more opened than that of Ca 2؉ -CIB1. Additional NMR experiments, such as chemical shift perturbation and methyl group solvent accessibility as measured by a nitroxide surface probe, were carried out to further characterize the structures of Ca 2؉ -CIB1 and Mg 2؉ -CIB1 as well as their interactions with the integrin ␣IIb cytoplasmic domain. NMR measurements of backbone amide proton slow motion (microsecond to millisecond) dynamics confirmed that the C-terminal helix of Ca 2؉ -CIB1 is displaced upon ␣IIb binding. The EF-hand III of both Ca 2؉ -CIB1 and Mg 2؉ -CIB1 was identified to be directly involved in the interaction of CIB1 with ␣IIb. Together, these data illustrate that CIB1 behaves quite differently from related EF-hand regulatory calcium-binding proteins, such as calmodulin or neuronal calcium sensor proteins.The calcium-and integrin-binding protein 1 (CIB1) is a member of the regulatory Ca 2ϩ -binding helix-loop-helix or EFhand protein family (1). CIB1 is a ubiquitous 191-residue (22 kDa) protein with several functions in cell signaling (2, 3). CIB1 has been reported to interact with a number of protein targets, including the platelet integrin ␣IIb subunit (4), sphingosine kinase 1 (5), p21-activated kinase (6), apoptosis signal-regulating kinase (7), polo-like protein kinases (8), and a recently reported new target in the regulation of cardiac hypertrophy, calcineurin B (9). The interaction of CIB1 with the integrin ␣IIb subunit has been studied extensively (10 -13). The integrin ␣IIb subunit usually associates with the integrin ␤3 subunit, and the heterodimeric ␣IIb␤3 protein is involved in both so-called "inside-out" and "outside-in" signaling pathways (3). CIB1 is believed to be capable of specifically binding to the ␣IIb cytoplasmic domain and dissociating the ␣IIb␤3 dimer, which in turn triggers integrin activation (11,12). The interactions between Ca 2ϩ -CIB1 and a fragment of the integrin ␣IIb subunit (residues 983-1008, hereafter referred to as the ␣IIb peptide) have been suggested to mainly involve a hydrophobic pocket in the C-domain of Ca 2ϩ -CIB1 with a dissociation constant in the submicromolar range (10).The calcium-bound CIB1 (Ca 2ϩ -CIB1) structure consists of four helix-loop-helix (EF-hand) Ca 2ϩ -binding m...

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Essential role of CIB1 in regulating PAK1 activation and cell migration

Cited by 79 publications

References 52 publications

CIB1 functions as a Ca ²⁺ -sensitive modulator of stress-induced signaling by targeting ASK1

CIB1 functions as a Ca ²⁺ -sensitive modulator of stress-induced signaling by targeting ASK1

Control of gastrula cell motility by the Goosecoid/Mix.1/ Siamois network: Basic patterns and paradoxical effects

Solution Structures of Ca2+-CIB1 and Mg2+-CIB1 and Their Interactions with the Platelet Integrin αIIb Cytoplasmic Domain

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Essential role of CIB1 in regulating PAK1 activation and cell migration

Cited by 79 publications

References 52 publications

CIB1 functions as a Ca 2+ -sensitive modulator of stress-induced signaling by targeting ASK1

CIB1 functions as a Ca 2+ -sensitive modulator of stress-induced signaling by targeting ASK1

Control of gastrula cell motility by the Goosecoid/Mix.1/ Siamois network: Basic patterns and paradoxical effects

Solution Structures of Ca2+-CIB1 and Mg2+-CIB1 and Their Interactions with the Platelet Integrin αIIb Cytoplasmic Domain

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CIB1 functions as a Ca ²⁺ -sensitive modulator of stress-induced signaling by targeting ASK1

CIB1 functions as a Ca ²⁺ -sensitive modulator of stress-induced signaling by targeting ASK1