The identification of a novel cDNA preferentially expressed in the olfactory-limbic system of the adult rat

Schaar, Dale; Varia, Monica; Elkabes, Stella; Ramakrishnan, Lakshmi; Dreyfus, Cheryl F.; Black, Ira B.

doi:10.1016/0006-8993(96)00176-x

Cited by 17 publications

(10 citation statements)

References 31 publications

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“…The remaining carboxy-terminal region of SLK displayed high homology to the LOK carboxy terminus of xPlkk1 and AT1-46, a cDNA clone encoding a protein of unknown function (50) (Fig. 1A).…”

Section: Resultsmentioning

confidence: 99%

Caspase 3 Cleavage of the Ste20-Related Kinase SLK Releases and Activates an Apoptosis-Inducing Kinase Domain and an Actin-Disassembling Region

Sabourin

Tamai²,

Seale

et al. 2000

Molecular and Cellular Biology

109

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We have demonstrated that a novel Ste20-related kinase, designated SLK, mediates apoptosis and actin stress fiber dissolution through distinct domains generated by caspase 3 cleavage. Overexpression of SLK in C2C12 myoblasts stimulated the disassembly of actin stress fibers and focal adhesions and induced apoptosis, as determined by annexin V binding and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling analysis. SLK was cleaved by caspase 3 in vitro and in vivo during c-Myc-, tumor necrosis factor alpha, and UV-induced apoptosis. Furthermore, cleavage of SLK released two domains with distinct activities: an activated N-terminal kinase domain that promoted apoptosis and cytoskeletal rearrangements and a C-terminus domain that disassembled actin stress fibers. Moreover, our analysis has identified a novel conserved region (termed the AT1-46 homology domain) that efficiently promotes stress fiber disassembly. Finally, transient transfection of SLK also activated the c-Jun N-terminal kinase signaling pathway. Our results suggest that caspase-activated SLK represents a novel effector of cytoskeletal remodeling and apoptosis.

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“…The remaining carboxy-terminal region of SLK displayed high homology to the LOK carboxy terminus of xPlkk1 and AT1-46, a cDNA clone encoding a protein of unknown function (50) (Fig. 1A).…”

Section: Resultsmentioning

confidence: 99%

Caspase 3 Cleavage of the Ste20-Related Kinase SLK Releases and Activates an Apoptosis-Inducing Kinase Domain and an Actin-Disassembling Region

Sabourin

Tamai²,

Seale

et al. 2000

Molecular and Cellular Biology

109

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“…Structurally, SLK is a serine-threonine kinase that contains an N-terminal kinase domain with the archetypal Ste20 consensus motif in kinase subdomain VIII (TPYWMAPE), a central coiled-coil domain and a C-terminal AT1-46 homology (ATH) domain (Figure 1.3) [70]. Although there is no known function of the central coiled-coil domain, it has been shown to contain potential SH3 binding sites and a putative caspase 3 cleavage site (DTQD) at positions 735 and 436, respectively [72][73][74]. The ATH domain however, exhibits a high degree of homology to the ATH1-46 protein of unknown function, and has also been found within both LOK and xPLKK1, suggesting that it may represent a novel motif [75].…”

Section: Discovery Of a Novel Kinasementioning

confidence: 99%

SLK-mediated phosphorylation of paxillin is required for focal adhesion turnover and cell migration

Baron

et al. 2012

Oncogene

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“…Further analysis showed that the central portion of SLK, from residues 339 ± 947 (Figure 2b) shared 70% identity with microtubule and nuclear associated protein (M-NAP). The remainder of SLK, from residues 788 ± 926, overlapping slightly with the M-NAP domain, displayed 63% identity to AT1-46 (Schaar et al, 1996) (Figure 2b). Interestingly, M-NAP and AT1-46 share signi®cant homology in the overlapping region.…”

Section: Slk a Ste20-related Kinasementioning

confidence: 99%

Induction of apoptosis by SLK, a Ste20-related kinase

1999

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We have cloned and characterized a novel murine Ste20-related kinase designated SLK. SLK displays high homology to the Ste20-related kinase LOK, and is more distantly related to MST1 and 2, both Ste20-like kinases. In addition, SLK displays high homology to microtubule and nuclear associated protein (M-NAP) and AT1-46, both of unknown function. SLK is ubiquitously expressed as multiple mRNAs in tissues and cell lines and is downregulated by mitogen depletion in di erentiating myoblasts. Biochemical characterization showed that SLK overexpression activates c-Jun amino-terminal kinase 1 (JNK1). However, in vitro kinase assays indicated that SLK was not activated in response to various growth factors or stress-inducing agents. Immuno¯uorescence studies revealed that SLK colocalized to distinct cytosolic domains, preferentially at the periphery of the cells. In addition, prolonged overexpression of SLK in cultured ®broblasts resulted in apoptosis as demonstrated by annexin-V and TUNEL staining. Our results suggest that SLK belongs to a new family of protein kinases, mediating activation of the stress response pathway through a novel signaling cascade.

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The identification of a novel cDNA preferentially expressed in the olfactory-limbic system of the adult rat

Cited by 17 publications

References 31 publications

Caspase 3 Cleavage of the Ste20-Related Kinase SLK Releases and Activates an Apoptosis-Inducing Kinase Domain and an Actin-Disassembling Region

Caspase 3 Cleavage of the Ste20-Related Kinase SLK Releases and Activates an Apoptosis-Inducing Kinase Domain and an Actin-Disassembling Region

SLK-mediated phosphorylation of paxillin is required for focal adhesion turnover and cell migration

Induction of apoptosis by SLK, a Ste20-related kinase

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