Dual-specificity protein kinases: will any hydroxyl do?

Lindberg, Richard A.; Quinn, Anne Marie; Hunter, Tony

doi:10.1016/0968-0004(92)90248-8

Cited by 230 publications

(177 citation statements)

References 21 publications

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“…A feature of dskl is that two protein bands were produced in SDS-PAGE by the dskl+ gene, and that their band intensity ratio was strikingly altered in G2-or M-phase arrested mutants. The fast migrating band (apparent M.W., 61 kd) was enhanced in G2-arrested cdc2 or cdc25 mutant cells, whereas the slowly migrating band (63 kd) was intensified in M-phase arrested disl, nda3, and Lindberg et al, 1992). It remains to be seen, however, whether a yet unidentified substrate of dskl might be tyrosine phosphorylated because MBP is the only substrate so far known among those examined for transphosphorylation by dskl.…”

Section: Discussionmentioning

confidence: 96%

A mitotic role for a novel fission yeast protein kinase dsk1 with cell cycle stage dependent phosphorylation and localization.

Takeuchi

Yanagida

1993

MBoC

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The fission yeast dskl+ gene, a multicopy suppressor for cold-sensitive disi mutants, encodes a novel 61-kd protein kinase. It is a phosphoprotein, and phosphoserine is the major phosphorylated amino acid. Hyperphosphorylation of dskl causes a mobility shift, resulting in two dskl-specific protein bands. The phosphorylation pattern is strikingly altered when cell cycle progression is delayed or arrested. The slowly migrating phosphorylated form is prominent in mitotically arrested cells, and the fast migrating form is enriched in interphasearrested cells. dskl is a protein kinase. It auto-phosphorylates as well as phosphorylates myelin basic protein (MBP). Phosphotyrosine as well as phosphoserine/threonine were found in autophosphorylation, but no tyrosine phosphorylation occurs when MBP was used as the substrate. The dskl immunoprecipitates from mitotically arrested cells have a several-fold higher kinase activity than that from wild type. The haploid gene disruptant is viable, indicating that the dskl+ gene is non-essential for viability. High dosage of dskl+, however, strongly delays the G2/M progression. Immunofluorescence microscopy using anti-dskl antibody shows that localization pattern of dskl protein strikingly alters depending on cell cycle stages. In G2-arrested cells, dskl locates in the cytoplasm, whereas in mitotically arrested cells, nuclear stain is intense. In wild-type cells, nuclear stain is seen only in mitotic cells. Hence dskl protein may play an important role in mitotic control by altering cellular location, degree of phosphorylation and kinase activity. We discuss possible roles of dskl kinase as an add-on regulator in mitosis.

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Section: Discussionmentioning

confidence: 96%

A mitotic role for a novel fission yeast protein kinase dsk1 with cell cycle stage dependent phosphorylation and localization.

Takeuchi

Yanagida

1993

MBoC

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“…The dual speci®city kinases (DSK) are unique in that they share the consensus kinases motifs of both Ser/ Thr and Tyr-kinases (Lindberg et al, 1992). Their ability to autophosphorylate Ser/Thr-as well as Tyrresidues in their amino acid sequences rather than those of the exogenous substrates initially identi®ed most of the dual speci®city kinases.…”

Section: Superfamily Of Dual-speci®city Kinasesmentioning

confidence: 99%

“…Their ability to autophosphorylate Ser/Thr-as well as Tyrresidues in their amino acid sequences rather than those of the exogenous substrates initially identi®ed most of the dual speci®city kinases. An earlier classi®cation of these kinases was based on their ability to dual-phosphorylate the exogenous substrates (Lindberg et al, 1992) and it divided these kinases into three groups: (1) kinases that show`true' dual speci®city by phosphorylating Tyr-and Thr-residues of exogenous substrates; (2) kinases that exhibit dual speci®city only through autophosphorylation; and (3) kinases that possess the structural motif characteristic of dual speci®city kinases. However, it has been observed that as the kinases belonging to group two and three get fully characterized, they turn out to be the`true dual speci®city kinases' of group one.…”

Section: Superfamily Of Dual-speci®city Kinasesmentioning

confidence: 99%

Signaling by dual specificity kinases

1998

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Dual speci®city kinases that phosphorylate the Thr-and Tyr-residues within the TXY motif of MAP-kinases of play a central role in the regulation of various processes of cell growth. These dual speci®city kinases also known as MAP kinase kinases are constituents of the sequential kinase signaling modules. Seven distinct mammalian MAP kinases kinases have been identi®ed. Some of the unique signaling properties of these kinases are discussed here.

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“…Few protein kinases can transfer the c-phosphate group from ATP to either aliphatic (serine or threonine) or aromatic (tyrosine) hydroxyl groups of amino acid side chains of their substrate proteins [1]. Best known among these so-called dual specificity kinases are the upstream kinases that activate members of the mitogen-activated protein kinase (MAPK) family by phosphorylating a conserved TXY motif in the activation loop [2,3].…”

Section: Introductionmentioning

confidence: 99%

Mechanism of dual specificity kinase activity of DYRK1A

et al. 2013

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The function of many protein kinases is controlled by the phosphorylation of a critical tyrosine residue in the activation loop. Dual specificity tyrosinephosphorylation-regulated kinases (DYRKs) autophosphorylate on this tyrosine residue but phosphorylate substrates on aliphatic amino acids. This study addresses the mechanism of dual specificity kinase activity in DYRK1A and related kinases. Tyrosine autophosphorylation of DYRK1A occurred rapidly during in vitro translation and did not depend on the non-catalytic domains or other proteins. Expression in bacteria as well as in mammalian cells revealed that tyrosine kinase activity of DYRK1A is not restricted to the co-translational autophosphorylation in the activation loop. Moreover, mature DYRK1A was still capable of tyrosine autophosphorylation. Point mutants of DYRK1A and DYRK2 lacking the activation loop tyrosine showed enhanced tyrosine kinase activity. A series of structurally diverse DYRK1A inhibitors was used to pharmacologically distinguish different conformational states of the catalytic domain that are hypothesized to account for the dual specificity kinase activity. All tested compounds inhibited substrate phosphorylation with higher potency than autophosphorylation but none of the tested inhibitors differentially inhibited threonine and tyrosine kinase activity. Finally, the related cyclin-dependent kinase-like kinases (CLKs), which lack the activation loop tyrosine, autophosphorylated on tyrosine both in vitro and in living cells. We propose a model of DYRK autoactivation in which tyrosine autophosphorylation in the activation loop stabilizes a conformation of the catalytic domain with enhanced serine/threonine kinase activity without disabling tyrosine phosphorylation. The mechanism of dual specificity kinase activity probably applies to related serine/threonine kinases that depend on tyrosine autophosphorylation for maturation. Structured digital abstract• CLK1 and CLK1 phosphorylate by protein kinase assay (View interaction)• HIPK2 and HIPK2 phosphorylate by protein kinase assay (View interaction)• DYRK1A phosphorylates SF3B1 by protein kinase assay (View interaction)• DYRK1A and DYRK1A phosphorylate by protein kinase assay (View interaction)

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Dual-specificity protein kinases: will any hydroxyl do?

Cited by 230 publications

References 21 publications

A mitotic role for a novel fission yeast protein kinase dsk1 with cell cycle stage dependent phosphorylation and localization.

A mitotic role for a novel fission yeast protein kinase dsk1 with cell cycle stage dependent phosphorylation and localization.

Signaling by dual specificity kinases

Mechanism of dual specificity kinase activity of DYRK1A

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