Proteolysis of Platelet Cortactin by Calpain

Huang, Cai; Tandon, Narendra N.; Greco, Nicholas J.; Ni, Yansong; Wang, Tony; Zhan, Xi

doi:10.1074/jbc.272.31.19248

Cited by 73 publications

(66 citation statements)

References 29 publications

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“…In addition, calpain-induced cleavage of FAK may be linked to specific tyrosine phosphorylation of FAK that leads to complex dissociation, perhaps releasing FAK and permitting its cleavage by calpain. Previous studies demonstrate that Src-mediated tyrosine phosphorylation of cortactin and the NR2 subunits of NMDA receptors influences the ability of v-Src-dependent Calpain and Caspase Cleavage of FAKthese proteins to be cleaved by calpain (49,50). It is therefore tempting to speculate that v-Src-dependent phosphorylation of FAK may influence the suitability of FAK to act as a substrate for calpain.…”

Section: Discussionmentioning

confidence: 96%

Cleavage of Focal Adhesion Kinase by Different Proteases during Src-regulated Transformation and Apoptosis

Carragher

Fincham

Riley

et al. 2001

Journal of Biological Chemistry

132

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Integrin-associated focal adhesion complexes provide the main adhesive links between the cellular actin cytoskeleton and the surrounding extracellular matrix. In vitro, cells utilize a complex temporal and spatially regulated mechanism of focal adhesion assembly and disassembly required for cell migration. Recent studies indicate that members of both calpain and caspase protease families can promote limited proteolytic cleavage of several components of focal adhesions leading to disassembly of these complexes. Such mechanisms that influence cell adhesion may be deregulated under pathological conditions characterized by increased cell motility, such as tumor invasion. v-Src-induced oncogenic transformation is associated with loss of focal adhesion structures and transition to a less adherent, more motile phenotype, while inactivating temperature-sensitive vSrc in serum-deprived transformed cells leads to detachment and apoptosis. In this report, we demonstrate that v-Src-induced disassembly of focal adhesions is accompanied by calpain-dependent proteolysis of focal adhesion kinase. Furthermore, inhibitors of calpain repress v-Src-induced focal adhesion disruption, loss of substrate adhesion, and cell migration. In contrast, focal adhesion loss during detachment and apoptosis induced after switching off temperature-sensitive v-Src in serum-deprived transformed cells is accompanied by caspase-mediated proteolysis of focal adhesion kinase. Thus, calpain and caspase differentially regulate focal adhesion turnover during Src-regulated cell transformation, motility, and apoptosis.The transforming viral Src gene (v-src) is associated with classic characteristics of oncogenic cell transformation, including deregulated growth control, cell rounding, and substrate detachment resulting from adhesion loss and disruption of the actin cytoskeleton (1-6). The stability of the actin cytoskeleton and adhesive properties of cells are mediated, at least in part, by focal adhesion complexes (7,8). Dynamic regulation of these adhesive links through assembly of focal adhesions at the leading edge of cells, coordinated with focal adhesion disassembly at the trailing edge, plays a key role in controlling cell migration (9). The mechanisms regulating turnover of focal adhesions are not well understood. However, a recent study suggests that proteolysis of specific components of the focal adhesion complex by the calpain family of proteolytic enzymes promotes disassembly of smooth muscle focal adhesions in response to collagen fragments (10). Furthermore, calpain activity has been implicated in promoting migration of Chinese hamster ovary cells (11). The calpains are defined as a well conserved family of intracellular, nonlysosomal calciumdependent cysteine proteases consisting of two ubiquitously expressed calpain isozymes, -calpain (calpain-I) and m-calpain (calpain-II) and several tissue-specific isoforms (12)(13)(14). Colocalization of calpain II with focal adhesion structures (15) and the identification of several focal adhesion protei...

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Section: Discussionmentioning

confidence: 96%

Cleavage of Focal Adhesion Kinase by Different Proteases during Src-regulated Transformation and Apoptosis

Carragher

Fincham

Riley

et al. 2001

Journal of Biological Chemistry

132

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“…The biochemical role of calpain in MC adhesion is undoubtedly complex. Given that calpain can cleave a number of cytoskeletal-associated proteins, such as talin, cortactin paxillin, and the ␤ 1 integrin cytoplasmic tail (39,40,50), the enzyme may have a role in both focal contact formation and reorganization of the actin cytoskeleton. In T cells it has been demonstrated that calpain cleaves PTP-1B, causing the relocation of the 42-kDa form of the phosphatase from the endoplasmic reticulum to sites of focal contacts via association with p130 cas .…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Calpain Is a Component of Nitric Oxide-Induced Down-Regulation of Human Mast Cell Adhesion

Forsythe

Befus

2003

The Journal of Immunology

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Nitric oxide is an important messenger that regulates mast cell activity by modifications to gene expression and intracellular pathways associated with exocytosis and adhesion. Integrin interactions with extracellular matrix components modulate an array of cell activities, including mediator production and secretion. To investigate the molecular mechanisms underlying NO regulation of mast cell function, we studied its effects on adhesion of a human mast cell line (HMC-1) to fibronectin (FN). The NO donors S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine strongly down-regulated the adhesion of HMC-1 to FN. Inhibitors of soluble guanylate cyclase and protein kinase G did not alter the response of cells to NO. A peroxynitrite scavenger did not affect modulation of adhesion by NO, nor could the effect of NO be mimicked by the peroxynitrite-producing compound 3-morpholinosydnonimine. NO donors inhibited the cysteine protease, calpain, while calpain inhibitors mimicked the effect of NO and led to a decrease in the ability of HMC-1 cells to adhere to FN. Thus, NO is an effective down-regulator of human mast cell adhesion. The mechanism for this action does not involve peroxynitrite or activation of soluble guanylate cyclase. Instead, a portion of NO-induced down-regulation of adhesion may be attributed to inhibition of the cysteine protease, calpain, an enzyme that has been associated with control of integrin activation in other cell types. The inhibition of calpain is most likely mediated via nitrosylation of its active site thiol group. Calpain may represent a novel therapeutic target for the regulation of mast cell activity in inflammatory disorders.

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“…In particular, actin cross-linking activity of cortactin and its calpain-mediated proteolysis are regulated by tyrosine phosphorylation (34,35). FAK is another major tyrosine kinase involved in cytoskeletal regulation (36).…”

Section: Discussionmentioning

confidence: 99%

Association of Tyrosine Phosphatase SHP-2 with F-actin at Low Cell Densities

Zhao

Peng

et al. 2001

Journal of Biological Chemistry

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SHP-2 is an intracellular SH2 domain-containing protein-tyrosine phosphatase with an essential role in cell signaling. Here we demonstrate that localization of SHP-2 is regulated by cell density in a cell adhesion-dependent manner. When cells were plated at low densities, SHP-2 was distributed in Triton X-100-insoluble fractions, whereas it was totally soluble when cells were plated at high densities or when low density cells approached confluency. In all cases, the total protein level of SHP-2 was not changed. Fluorescent cell staining revealed that SHP-2 was co-localized with actin stress fibers to the cell peripheral at low cell densities but was diffused in the entire cytoplasm at high cell densities. Transient transfection of cells with truncated forms of SHP-2 demonstrated that the catalytic domain of the enzyme was responsible for the density-regulated distribution of SHP-2, but the catalytic activity was not required. An in vitro co-sedimentation study demonstrated direct binding of full-length and SH2 domaintruncated forms of SHP-2 to F-actin. The data indicate that SHP-2 is regulated by cell density and that it may have a role in assembling and disassembling of the actin network.

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Proteolysis of Platelet Cortactin by Calpain

Cited by 73 publications

References 29 publications

Cleavage of Focal Adhesion Kinase by Different Proteases during Src-regulated Transformation and Apoptosis

Cleavage of Focal Adhesion Kinase by Different Proteases during Src-regulated Transformation and Apoptosis

Inhibition of Calpain Is a Component of Nitric Oxide-Induced Down-Regulation of Human Mast Cell Adhesion

Association of Tyrosine Phosphatase SHP-2 with F-actin at Low Cell Densities

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