Protein kinase regulation: insights from crystal structure analysis

Morgan, David; Bondt, H.L. De

doi:10.1016/0955-0674(94)90142-2

Cited by 98 publications

(51 citation statements)

References 63 publications

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“…This activating phosphorylation is catalyzed by CDK-activating kinases (CAKs; Kaldis, 1999). Crystal structure analyses of monomeric CDK2 showed that the T-loop region blocks access of the potential substrates to the catalytic site (Morgan and De Bondt, 1994). Upon phosphorylation of Thr160 by CAK, the T-loop moves away and the cyclin A-CDK2 complex becomes fully active (Jeffrey et al, 1995;Russo et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

The Plant-Specific Kinase CDKF;1 Is Involved in Activating Phosphorylation of Cyclin-Dependent Kinase-Activating Kinases in Arabidopsis

et al. 2004

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Cyclin-dependent kinases (CDKs) play essential roles in coordinate control of cell cycle progression. Activation of CDKs requires interaction with specific cyclin partners and phosphorylation of their T-loops by CDK-activating kinases (CAKs). The Arabidopsis thaliana genome encodes four potential CAKs. CAK2At (CDKD;3) and CAK4At (CDKD;2) are closely related to the vertebrate CAK, CDK7/p40MO15; they interact with cyclin H and phosphorylate CDKs, as well as the C-terminal domain (CTD) of the largest subunit of RNA polymerase II. CAK1At (CDKF;1) shows cyclin H-independent CDK-kinase activity and can activate a heterologous CAK, Mcs6, in fission yeast. In Arabidopsis, CAK1At is a subunit of a protein complex of 130 kD, which phosphorylates the T-loop of CAK2At and CAK4At and activates the CTD-kinase activity of CAK4At in vitro and in root protoplasts. These results suggest that CAK1At is a novel CAK-activating kinase that modulates the activity of CAK2At and CAK4At, thereby controlling CDK activities and basal transcription in Arabidopsis

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Section: Introductionmentioning

confidence: 99%

The Plant-Specific Kinase CDKF;1 Is Involved in Activating Phosphorylation of Cyclin-Dependent Kinase-Activating Kinases in Arabidopsis

et al. 2004

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“…While the ATPase/helicases were the first components of TFIIH shown to be involved in DNA damage repair (3,4), additional subunits of the core complex prove to be required for repair as well (5)(6)(7)(8)(9). The human counterpart of TFIIK, known as CAK, was originally identified on the basis of its capacity to activate cyclindependent kinases involved in cell cycle control through phosphorylation of a key threonine residue in vitro (10,11). Genetic studies in yeast, while supporting the essential role of TFIIH in RNA polymerase II transcription and in phosphorylation of the C-terminal domain, have raised doubts as to the requirement of TFIIK for cyclin-dependent protein kinase function in vivo (12).…”

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confidence: 99%

Genes For Tfb2, Tfb3, and Tfb4 Subunits of Yeast Transcription/Repair Factor IIH

Feaver

Henry

Wang

et al. 1997

Journal of Biological Chemistry

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Genes for the Tfb2, Tfb3, and Tfb4 subunits of yeast RNA polymerase transcription factor IIH (TFIIH) are described. All three genes are essential for cell viability, and antibodies against Tfb3 specifically inhibit transcription in vitro. A C-terminal deletion of Tfb2 caused a defect in nucleotide excision repair, as shown by UV sensitivity of the mutant strain and loss of nucleotide excision repair activity in cell extracts (restored by the addition of purified TFIIH). An interaction between Tfb3 and the Kin28 subunit of TFIIH was detected by the two-hybrid approach, consistent with a role for Tfb3 in linking kinase and core domains of the factor. The deduced amino acid sequence of Tfb2 is similar to that of the 52-kDa subunit of human TFIIH, while Tfb3 is identified as a RING finger protein homologous to the 36-kDa subunit of murine CAK (cyclin-dependent kinase activating kinase) and to the 32-kDa subunit of human TFIIH. Tfb4 is homologous to p34 of human TFIIH and is identified as the weakly associated 37-kDa subunit of the yeast factor. These and other findings reveal a oneto-one correspondence and high degree of sequence similarity between the entire set of yeast and human TFIIH polypeptides.

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“…Hence, phosphorylation of these residues often increases the intrinsic catalytic activities of kinases (29), as is true for Y1162 in the insulin receptor kinase (13). For Jak family proteins, two adjacent tyrosine residues within the activation loop have been implicated in the control of their catalytic activities.…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation of Human Jak3 at Tyrosines 904 and 939 Positively Regulates Its Activity

Cheng

Ross

Frost

et al. 2008

Molecular and Cellular Biology

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Janus tyrosine kinase 3 (Jak3) is essential for signaling by interleukin-2 (IL-2) family cytokines and proper immune function. Dysfunctional regulation of Jak3 may result in certain disease states. However, the molecular mechanisms governing Jak3 activation are not fully understood. In this study, we used a functionalproteomics approach to identify two novel tyrosine phosphorylation sites within Jak3, Y904 and Y939, which are conserved among Jak family proteins. By using phosphospecific antibodies, both residues were observed to be rapidly induced by stimulation of cells with IL-2 or other ␥c cytokines. Mechanistic studies indicated that Y904 and Y939 regulate Jak3 activities. A phenylalanine substitution at either site greatly reduced Jak3 kinase activity in vitro and its ability to phosphorylate signal transducer and activator of transcription 5 (Stat5) in vivo, suggesting that phosphorylation of these previously unrecognized residues positively regulates Jak3 activity. Y904 and Y939 were required for optimal ATP usage by Jak3, while phosphorylation of Y939 preferentially promoted Stat5 activity in intact cells. Together, these findings demonstrate positive functional roles for two novel Jak3 phosphoregulatory sites which may be similarly important for other Jak family members. Identification of these sites also provides new therapeutic opportunities to modulate Jak3 function.

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Protein kinase regulation: insights from crystal structure analysis

Cited by 98 publications

References 63 publications

The Plant-Specific Kinase CDKF;1 Is Involved in Activating Phosphorylation of Cyclin-Dependent Kinase-Activating Kinases in Arabidopsis

The Plant-Specific Kinase CDKF;1 Is Involved in Activating Phosphorylation of Cyclin-Dependent Kinase-Activating Kinases in Arabidopsis

Genes For Tfb2, Tfb3, and Tfb4 Subunits of Yeast Transcription/Repair Factor IIH

Phosphorylation of Human Jak3 at Tyrosines 904 and 939 Positively Regulates Its Activity

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