CDK1-mediated Phosphorylation of Abi1 Attenuates Bcr-Abl-induced F-actin Assembly and Tyrosine Phosphorylation of WAVE Complex during Mitosis

Zhuang, Chun-Mei; Tang, Hong; Cobos, Everardo; Tao, Yunxia; Dai, Zhenwen

doi:10.1074/jbc.m111.281139

Cited by 17 publications

(23 citation statements)

References 43 publications

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“…There is also a shift in the dominance of different cortical actin nucleators at the onset of mitosis, from the ARP2/3 complex to formins 14,35,36 . For cells enter ing mitosis in culture, this is apparent from the loss of lamellipodia, which are actinbased membrane pro trusions that are generated by branched actin filament nucleation downstream of Rac, the SCAR/WAVE com plex [37][38][39] and the ARP2/3 complex. Although the extent to which residual ARP2/3 activity contributes to the gener ation of mitotic structures is currently unclear 14,35,36 , this loss of lamellipodial actin is accompan ied by the activ ation of the forminbased actin nucleator Diaphanous (DIA) 14 , which drives the assembly of a cortical net work of actin filaments.…”

Section: Adherens Junctionsmentioning

confidence: 99%

Coupling changes in cell shape to chromosome segregation

Ramkumar

Baum

2016

Nat Rev Mol Cell Biol

129

132

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Animal cells undergo dramatic changes in shape, mechanics and polarity as they progress through the different stages of cell division. These changes begin at mitotic entry, with cell-substrate adhesion remodelling, assembly of a cortical actomyosin network and osmotic swelling, which together enable cells to adopt a near spherical form even when growing in a crowded tissue environment. These shape changes, which probably aid spindle assembly and positioning, are then reversed at mitotic exit to restore the interphase cell morphology. Here, we discuss the dynamics, regulation and function of these processes, and how cell shape changes and sister chromatid segregation are coupled to ensure that the daughter cells generated through division receive their fair inheritance.

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Section: Adherens Junctionsmentioning

confidence: 99%

Coupling changes in cell shape to chromosome segregation

Ramkumar

Baum

2016

Nat Rev Mol Cell Biol

129

132

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“…Abl localizes to the cell periphery with the WRC and phosphorylates both WAVE and ABI [50, 51]. The ABI SH3 domain and Proline-rich sequences are required for Abl interaction with the other WRC members and for Abl phosphorylation of WAVE2 [51-54]. A “kinase dead” Abl mutant, in which the activation loop lysine that coordinates interaction with ATP is mutated to arginine, exhibits reduced interaction with the WRC [53].…”

Section: Tyrosine Phosphorylation Of the Wrcmentioning

confidence: 99%

“…3 [54]). CDK1 is activated at the end of interfase by A-type cyclins and promotes mitotic entry [67].…”

Section: Serine/threonine Phosphorylation Of the Wrcmentioning

confidence: 99%

“…Following nuclear envelope breakdown and cyclin A degradation, CDK1 is activated by B-type cyclins and promotes mitotic progression (reviewed in [68]). CDK1 phosphorylation of ABI1 inhibits tyrosine phosphorylation of ABI1 and WAVE2 [54]. Indeed, mitotic cells do not exhibit tyrosine phosphorylation of WAVE2 or ABI1 [54].…”

Section: Serine/threonine Phosphorylation Of the Wrcmentioning

confidence: 99%

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Phosphoregulation of the WAVE regulatory complex and signal integration

Mendoza

2013

Seminars in Cell & Developmental Biology

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The WAVE2 Regulatory Complex (WRC) induces actin polymerization by activating the actin nucleator Arp2/3. Polymerizing actin pushes against the cell membrane and induces dramatic edge protrusions. In order to properly control such changes in cell morphology and function, cells have evolved multiple methods to tightly regulate WRC and Arp2/3 activity in space and time. Of these mechanisms, phosphorylation plays a fundamental role in transmitting extracellular and intracellular signals to the WRC and the actin cytoskeleton. This review discusses the phosphorylation-based regulatory inputs into the WRC. Signaling pathways that respond to growth factors, chemokines, hormones, and extracellular matrix converge upon the WAVE and ABI components of the WRC. The Abl, Src, ERK, and PKA kinases promote complex activation through a WRC conformation change that permits interaction with the Arp2/3 complex and through WRC translocation to the cell edge. The neuron-specific CDK5 and constitutively active CK2 kinases inhibit WRC activation. These regulatory signals are integrated in space and time as they coalesce upon the WRC. The combination of WRC phosphorylation events and WRC activity is controlled by stimulus, cell type, and cell cycle-specific pathway activation and via pathway cross-inhibition and cross-activation.

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“…ABI1 binding facilitates Abl oligomerization and autophosphorylation, leading to enhanced phosphorylation of Abl substrates (38 -40). Interaction with ABI1 may link Abl kinases to remodeling of the actin cytoskeleton (41)(42)(43). Another example is the Ras effector protein RIN1, which engages both the Abl SH2 and SH3 domains (44), leading to kinase activation through a domain displacement mechanism.…”

Section: Regulation Of Abl Kinase Activity By Phosphorylation and Intmentioning

confidence: 99%

Structure and Dynamic Regulation of Abl Kinases*

Panjarian

Iacob

Chen

et al. 2013

Journal of Biological Chemistry

108

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The c-abl proto-oncogene encodes a unique protein-tyrosine kinase (Abl) distinct from c-Src, c-Fes, and other cytoplasmic tyrosine kinases. In normal cells, Abl plays prominent roles in cellular responses to genotoxic stress as well as in the regulation of the actin cytoskeleton. Abl is also well known in the context of Bcr-Abl, the oncogenic fusion protein characteristic of chronic myelogenous leukemia. Selective inhibitors of Bcr-Abl, of which imatinib is the prototype, have had a tremendous impact on clinical outcomes in chronic myelogenous leukemia and revolutionized the field of targeted cancer therapy. In this minireview, we focus on the structural organization and dynamics of Abl kinases and how these features influence inhibitor sensitivity. Structural Overview of the c-Abl Kinase CoreThe kinase core of the c-Abl protein has a domain organization similar to that of the Src family kinases, with sequential Src homology (SH) 3 3 and SH2 domains, an SH2/kinase linker, and a bilobed kinase domain (Fig. 1). This core is flanked by an N-terminal "cap" (N-cap) region with a signal sequence for myristoylation, which serves dual roles in regulation of kinase activity and in membrane localization. C-terminal to the kinase domain is a long region of Ͼ600 amino acids encoded by a single exon, which controls interaction of Abl with other SH3-containing proteins and the actin cytoskeleton. This region also regulates nuclear-cytoplasmic shuttling of the kinase (1-4). These key structural and regulatory features are discussed in detail below. The Myristoylated N-cap Is Critical for Down-regulation of AblThe N-cap is ϳ80 amino acids in length and is myristoylated in the 1b splice variant of Abl (5). The first crystal structure of the Abl core (residues 1-531) revealed that this N-terminal myristic acid group binds a deep hydrophobic pocket in the C-terminal lobe (C-lobe) of the kinase domain ( Fig. 1) (6). Binding of the myristoyl group into this pocket induces a bend in C-lobe helix ␣I, allowing the SH2 domain to dock onto the C-lobe of the kinase domain (Fig. 2). Interaction of the myristoylated N-cap with the C-lobe is critical to maintenance of the autoinhibited state, as mutation of the myristoylation signal sequence results in a highly active kinase (7). Interestingly, small molecules that bind to this site also modulate kinase activity, supporting an allosteric connection between this regulatory pocket and the kinase active site (8 -11).In addition to binding the C-lobe of the kinase domain, the N-cap also influences kinase regulation via the SH3 and SH2 domains. Although the N-cap region was disordered in the first crystal structure of the c-Abl core, a more recent structure with a modified N-cap revealed that Ser 69 (numbered according to Protein Data Bank (PDB) code 2FO0) 4 is phosphorylated and contacts the short connector joining the SH3 and SH2 domains. Mutation of Ser 69 increased Abl activity, identifying this site as a potential input for regulatory kinases (12). Additional contacts were observed between N...

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CDK1-mediated Phosphorylation of Abi1 Attenuates Bcr-Abl-induced F-actin Assembly and Tyrosine Phosphorylation of WAVE Complex during Mitosis

Cited by 17 publications

References 43 publications

Coupling changes in cell shape to chromosome segregation

Coupling changes in cell shape to chromosome segregation

Phosphoregulation of the WAVE regulatory complex and signal integration

Structure and Dynamic Regulation of Abl Kinases*

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