Alternative Splicing of STY, a Nuclear Dual Specificity Kinase

Duncan, Peter I.; Howell, Brian W.; Marius, Ricardo; Drmanic, Suzana; Douville, E M; Bell, John C.

doi:10.1074/jbc.270.37.21524

Cited by 68 publications

(106 citation statements)

References 30 publications

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“…Using the full-length cDNA as a probe, two transcripts of about 3.2 and 1.8 kb were detected. This result agreed with previous observations made in several cell lines and tissues [1,2,4,10]. The 3.2 kb band corresponded to an incompletely processed transcript that accumulated in the nucleus [4].…”

Section: Expression Of Clk/sty Clk2 Clk3 and Clk4 In Hmbatreated Musupporting

confidence: 92%

“…This result agreed with previous observations made in several cell lines and tissues [1,2,4,10]. The 3.2 kb band corresponded to an incompletely processed transcript that accumulated in the nucleus [4]. The 1.8 kb band exhibited a diffuse pattern probably due to co-migration of two alternative spliced forms [4].…”

Section: Expression Of Clk/sty Clk2 Clk3 and Clk4 In Hmbatreated Musupporting

confidence: 92%

“…What clearly differentiates clk/STY from other kinases is a dual-specificity to phosphorylate tyrosine as well as serine-threonine residues [1,2,4]. Clk/STY is considered an important member of the LAMMER subfamily of protein kinases on behalf of a conserved amino acid motif reading "EHLAMMERILG", that is found at the catalytic subdomain X [5].…”

Section: Introductionmentioning

confidence: 99%

“…Besides, clk/STY regulates its own splicing leading to two alternative spliced transcripts encoding a full-length catalytically active kinase and a truncated form lacking the kinase domain and incapable of phosphorylation [4,13]. When clk/STY is overexpressed in cultured cells, the kinase together with SR proteins is homogeneously localized throughout the nucleus.…”

Section: Introductionmentioning

confidence: 99%

“…As in the case of clk/STY, the clk2, 3 and 4 kinases also show alternative splicing and the exon/intron boundaries of the originally described "exon B" [4] are conserved [8,10]. Inclusion of the "B-like exon" in clk2, 3 and 4 produces a full-length catalytically active protein.…”

Section: Introductionmentioning

confidence: 99%

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Protein kinase clk/STY is differentially regulated during erythroleukemia cell differentiation: a bias toward the skipped splice variant characterizes postcommitment stages

et al. 2005

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Clk/STY is a LAMMER protein kinase capable to phosphorylate serine/arginine-rich (SR) proteins that modulate premRNA splicing. Clk/STY alternative splicing generates transcripts encoding a full-length kinase and a truncated catalytically inactive protein. Here we showed that clk/STY, as well as other members of the family (e.g. clk2, clk3 and clk4), are up-regulated during HMBA-induced erythroleukemia cell differentiation. mRNAs coding for the full-length and the truncated forms were responsible for the overall increased expression. In clk/STY, however, a switch was observed for the ratio of the two alternative spliced products. In undifferentiated cells the full-length transcript was more abundant whereas the transcript encoding for the truncated form predominated at latter stages of differentiation. Surprisingly, overexpression of clk/STY did not alter the splicing switch upon differentiation in MEL cells. These results suggest that clk/STY might contribute to control erythroid differentiation by a mechanism that implicates a balance between these two isoforms.

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Section: Expression Of Clk/sty Clk2 Clk3 and Clk4 In Hmbatreated Musupporting

confidence: 92%

Section: Expression Of Clk/sty Clk2 Clk3 and Clk4 In Hmbatreated Musupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Protein kinase clk/STY is differentially regulated during erythroleukemia cell differentiation: a bias toward the skipped splice variant characterizes postcommitment stages

et al. 2005

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Functions ofSRPK,CLKandDYRKkinases in stem cells, development, and human developmental disorders

Hogg,

Findlay

2023

FEBS Letters

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Human developmental disorders encompass a wide range of debilitating physical conditions and intellectual disabilities. Perturbation of protein kinase signalling underlies the development of some of these disorders. For example, disrupted SRPK signalling is associated with intellectual disabilities, and the gene dosage of DYRKs can dictate the pathology of disorders including Down's syndrome. Here, we review the emerging roles of the CMGC kinase families SRPK, CLK, DYRK, and sub‐family HIPK during embryonic development and in developmental disorders. In particular, SRPK, CLK, and DYRK kinase families have key roles in developmental signalling and stem cell regulation, and can co‐ordinate neuronal development and function. Genetic studies in model organisms reveal critical phenotypes including embryonic lethality, sterility, musculoskeletal errors, and most notably, altered neurological behaviours arising from defects of the neuroectoderm and altered neuronal signalling. Further unpicking the mechanisms of specific kinases using human stem cell models of neuronal differentiation and function will improve our understanding of human developmental disorders and may provide avenues for therapeutic strategies.

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Alternative promoter usage generates multiple evolutionarily conserved isoforms of Drosophila DOA kinase

Kpebe

Rabinow

2008

Genesis

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The unique LAMMER (or Clk) protein kinase of Drosophila is encoded at the Doa locus. To better understand the pleiotropic effects of Doa mutations, we describe the structure and expression of the multiple RNA and protein products of the locus, as well as their evolutionary conservation among Drosophila. The gene produces at least six different protein isoforms, primarily through alternative promoter usage, generating kinases with virtually identical catalytic domains but variable N-terminal noncatalytic domains. The single known alternative splicing event generates a kinase with the insertion of six additional amino-acids in the catalytic domain. Two independent predicted genes nested within Doa introns actually encode additional alternative N-termini of the locus. An alternative polyadenylation site utilized exclusively during early embryogenesis generates a transcript with a short half-life, apparently to ensure a "burst" of kinase expression at the onset of development. Ecdysone induction of Doa transcripts affects all isoforms during pupariation. Finally, extensive conservation of amino-acid sequences of both the catalytic and N-terminal noncatalytic exons observed in alignments between D. melanogaster exons and the genome sequences of 11 other Drosophila species suggest that the multiple isoforms serve important and nonredundant functions.

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Alternative Splicing of STY, a Nuclear Dual Specificity Kinase

Cited by 68 publications

References 30 publications

Protein kinase clk/STY is differentially regulated during erythroleukemia cell differentiation: a bias toward the skipped splice variant characterizes postcommitment stages

Protein kinase clk/STY is differentially regulated during erythroleukemia cell differentiation: a bias toward the skipped splice variant characterizes postcommitment stages

Functions ofSRPK,CLKandDYRKkinases in stem cells, development, and human developmental disorders

Alternative promoter usage generates multiple evolutionarily conserved isoforms of Drosophila DOA kinase

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