Nuclear-cytoplasmic shuttling of C-ABL tyrosine kinase

Taagepera, Salme; McDonald, D; Loeb, Jonathan E.; Whitaker, Laura; McElroy, Anita K.; Wang, Jean Y. J.; Hope, Thomas J.

doi:10.1073/pnas.95.13.7457

Cited by 279 publications

(248 citation statements)

References 40 publications

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“…c-Abl binding is mediated by the SH3 domain of Bin1 (Kadlec and Pendergast, 1997), which is dispensable for its association with c-Myc (Sakamuro et al, 1996;Elliott et al, 1999). A fraction of c-Abl in cells is reported to be activated at focal adhesions where integrins are located (Lewis et al, 1996;Taagepera et al, 1998), so since apoptosis by c-Myc is in¯uenced by integrin signals (Crouch et al, 1996) there may be links via this route to c-Abl activation. How Bin1 and c-Abl in¯uence the action of each other in proliferation, di erentiation, and apoptosis remains to be determined, however.…”

Section: Role Of Interaction With the Cell Fate Adaptor Protein Bin1mentioning

confidence: 99%

Mechanisms of apoptosis by c-Myc

1999

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Section: Role Of Interaction With the Cell Fate Adaptor Protein Bin1mentioning

confidence: 99%

Mechanisms of apoptosis by c-Myc

1999

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“…Physiological functions dependent on c-Abl remain largely elusive. Certain insights have been derived from the findings that c-Abl shuttles between the nucleus and the cytoplasm (Taagepera et al, 1998;Wang, 2000). In contrast, oncogenic forms of Abl, including v-Abl and Bcr-Abl, localize exclusively in the cytoplasm and induce cellular transformation by promoting proliferation and inhibiting apoptotic cell death (Wetzler et al, 1993;Wang, 2000;Pendergast, 2002).…”

Section: Introductionmentioning

confidence: 99%

TTK/Mps1 controls nuclear targeting of c-Abl by 14-3-3-coupled phosphorylation in response to oxidative stress

et al. 2008

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Upon exposure to genotoxic stress, the c-Abl tyrosine kinase is released from cytoplasmic 14-3-3 proteins and then is targeted to the nucleus. Phosphorylation of Thr735 in c-Abl is critical for binding to 14-3-3; however, kinases responsible for this phosphorylation are unknown. Here, we identify CLK1, CLK4, MST1, MST2 and TTK (also known as Mps1) as novel Thr735 kinases in vitro by expression cloning strategy using phosphospecific antibody. We also demonstrate that ectopic expression of these kinases is capable for phosphorylation of Thr735 in cells. Importantly, upon exposure to oxidative stress, phosphorylation of Thr735 is transiently upregulated, and the status of this phosphorylation remains unchanged in cells silenced for CLK1, CLK4, MST1 or MST2. By contrast, knockdown of TTK attenuates phosphorylation of Thr735, suggesting that TTK is a physiological kinase that phosphorylates Thr735. In concert with these results, we show that, in cells silenced for TTK, c-Abl is accumulated in the nucleus even in unstressed condition and no further targeting into the nucleus occurs after oxidative stress. Moreover, nuclear entrapment of c-Abl by knocking down TTK enhances oxidative stress-induced apoptosis. These findings provide evidence that TTK phosphorylates c-Abl at Thr735 and that this phosphorylation is of importance to the cytoplasmic sequestration of c-Abl.

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“…In the nucleus, c-Abl protein is known to be activated in response to DNA damage and contributes to apoptosis (Wang, 2000). Cytoplasmic c-Abl is associated with growth factor receptor signaling that can affect cell mobility and cell adhesion (Taagepera et al, 1998). Several studies have shown that c-Abl contains intramolecular interactions that provide autoinhibitory mechanisms (Pendergast, 2002;Pluk et al, 2002;Hantschel et al, 2003).…”

Section: Introductionmentioning

confidence: 99%