A novel kinase, AATYK induces and promotes neuronal differentiation in a human neuroblastoma (SH-SY5Y) cell line

Raghunath, Manchala; Patti, Ratnakar; Bannerman, Peter; Lee, Clement; Baker, Stacey J.; Sutton, Leslie N.; Phillips, Peter C.B.; Reddy, C. Devendranath

doi:10.1016/s0169-328x(00)00048-6

Cited by 60 publications

(58 citation statements)

References 31 publications

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“…These results are consistent with earlier studies that used a neuroblastoma cell line (Raghunath et al, 2000) and suggest that the AATYK protein is upregulated during RA-induced terminal di erentiation of neuronal cells. In addition, this increase in AATYK expression is remarkably similar to that reported by us ,d).…”

Section: Discussionsupporting

confidence: 93%

“…These results suggest that AATYK is normally expressed in adult brain and is not necessarily always associated with apoptotic death of the neurons. In fact, previous studies by Raghunath et al (2000) have shown that ectopic AATYK expression was able to promote the di erentiation of SH-SY5Y adrenergic neuroblastoma cells without e ecting their survival.…”

Section: Discussionmentioning

confidence: 96%

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Characterization of an alternatively spliced AATYK mRNA: Expression pattern of AATYK in the brain and neuronal cells

et al. 2001

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 96%

Characterization of an alternatively spliced AATYK mRNA: Expression pattern of AATYK in the brain and neuronal cells

et al. 2001

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“…The pCMV-p16 and the pCMV-CDK2-dn vectors were provided by E Harlow (Koh et al, 1995;Serrano et al, 1993;van den Heuvel and Harlow, 1993). The ptTAs vector is a pCMV vector kindly provided by C Lee and EP Reddy (Raghunath et al, 2000). The ptTAs-HA-p130, pcDNAI-E1A wild type (12S) and pcDNAI-E1A mutant 928/961(mt1) (12S) plasmids were described previously (ParrenÄ o et al, 2000).…”

Section: Plasmidsmentioning

confidence: 99%

E1A modulates phosphorylation of p130 and p107 by differentially regulating the activity of G1/S cyclin/CDK complexes

et al. 2001

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We have previously shown that the adenoviral 12S E1A protein modulates the phosphorylation status of p130 and p107 without apparent changes in the cell cycle dependent phosphorylation of the retinoblastoma protein.Here we report on the mechanisms by which E1A modi®es di erentially the phosphorylation status of pocket proteins. In human U-2 OS osteosarcoma cells transiently expressing E1A, ectopic expression of D-type cyclins alone or combined, but not cyclins E and/or A, fully rescues E1A-mediated block in hyperphosphorylation of p130 to form 3. However, cyclins E and A, individually or together, induce hyperphosphorylation of p130 to species with intermediate mobility. Phosphopeptide maps indicate that E1A inhibits phosphorylation of sites phosphorylatable by CDKs. One of these sites is Ser-1044. The e ects of blocking the activities of endogenous and exogenous cyclins with p16 and dominant negative CDK2 in E1A expressing cells further indicate that p130 is phosphorylated by both D-type cyclin and cyclin E/CDK complexes and that E1A modulates the activity of these G1/S CDKs by independent mechanisms. Stable expression of E1A in MC3T3-E1 cells leads to downregulation of D-type cyclins, and upregulation of cyclins E and A. This is accompanied by increased CDK2 kinase activity. Downregulation of D-type cyclins in these cells correlates with a block on both p130 hyperphosphorylation to form 3 and hyperphosphorylation of p107. This is rescued by Dtype cyclins but not by cyclin E. In addition, we show that the upregulation of cyclins E and A is at least partially dependent on an intact pocket protein/E2F pathway, but downregulation of D-type cyclins is not. Moreover, we provide evidence that while the lack of a functional pRB pathway also results in a block on hyperphosphorylation of p130 to form 3, this is not su cient to induce constitutive expression of p130 form 2b. Oncogene (2001) 20, 4793 ± 4806.

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“…1 It is predominantly expressed at high levels in different regions of the brain, whereas at relatively low levels in other tissues including heart, lung, kidney, and skeletal muscle. [1][2][3][4] AATK contains a tyrosine kinase domain at the N-terminus and a proline-rich SH3-binding motif consisting of 16 PXXP motifs at the C-terminus. Two isoforms of AATK have been reported and referred to as AATKA and AATKB.…”

mentioning

confidence: 99%

Apoptosis-associated tyrosine kinase 1 inhibits growth and migration and promotes apoptosis in melanoma

Rubin

2014

Laboratory Investigation

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Apoptosis-associated tyrosine kinase 1 (AATK1) was initially identified as a protein that was dramatically overexpressed during growth arrest and apoptosis of 32Dcl myeloblastic leukemia cells. AATK is expressed in different regions of the brain and may have a role in normal nervous system development by its dual functions of enhancing apoptosis of mature granule cells and promoting terminal neuronal differentiation of developing neurons. However, its function in cancer has never been studied. Melanoma is a tumor composed of transformed cells within the melanocyte lineage deriving from the embryonic neural crest. It has been shown that developmental pathways in neural crest cells have a direct bearing on melanoma formation and human metastatic melanoma cells express a dedifferentiated phenotype. We found that the expression levels of AATK are lower in metastatic melanoma cell lines compared with primary melanoma cell lines and normal human melanocytes. We found that depletion of AATK mRNA in metastatic melanoma cell lines enhanced cell migration in cell line derived from metastatic melanomas. Overexpression of AATK inhibited cell proliferation, colony formation, and promoted apoptosis in melanoma cell lines derived from primary and metastatic melanomas. Signal transduction pathway analysis revealed that Src is involved in regulating AATK. Our results demonstrate for the first time that AATK inhibits cell proliferation, colony formation, and migration, and also promotes apoptosis in melanoma cells.

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A novel kinase, AATYK induces and promotes neuronal differentiation in a human neuroblastoma (SH-SY5Y) cell line

Cited by 60 publications

References 31 publications

Characterization of an alternatively spliced AATYK mRNA: Expression pattern of AATYK in the brain and neuronal cells

Characterization of an alternatively spliced AATYK mRNA: Expression pattern of AATYK in the brain and neuronal cells

E1A modulates phosphorylation of p130 and p107 by differentially regulating the activity of G1/S cyclin/CDK complexes

Apoptosis-associated tyrosine kinase 1 inhibits growth and migration and promotes apoptosis in melanoma

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