Abstract
The cyclin-dependent kinases are key cell cycle regulators whose activation is required for passage from one cell cycle phase to the next. In mammalian cells, CDK2 has been implicated in control of the G1 and S phases. We have used a two-hybrid protein interaction screen to identify cDNAs encoding proteins that can interact with CDK2. Among those identified was a protein (KAP), which contained the HCXX-XXGR motif characteristic of protein tyrosine phosphatases. KAP showed phosphatase activity toward substrates containing either phosphotyrosine or phosphoserine residues. Since KAP is not significantly similar to known phosphatases beyond the catalytic core motif, it represents an additional class of dual specificity phosphatase. KAP interacted with cdc2 and CDK2 in yeast. In mammalian cells, KAP also associated with cdc2 and CDK2 but showed a preference for cdc2. The ability of KAP to bind multiple cyclin-dependent kinases suggests that it may play a role in cell cycle regulation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Base Sequence
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CDC2 Protein Kinase / metabolism
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CDC2-CDC28 Kinases*
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Cell Cycle Proteins*
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase Inhibitor Proteins
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Cyclin-Dependent Kinases*
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DNA, Complementary / genetics
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Dual-Specificity Phosphatases
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Escherichia coli / genetics
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G1 Phase / physiology
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HeLa Cells
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Humans
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Molecular Sequence Data
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Phosphoric Monoester Hydrolases / genetics
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Phosphoric Monoester Hydrolases / metabolism*
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Phosphorylation
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Protein Kinases / metabolism*
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Protein Serine-Threonine Kinases*
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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S Phase / physiology
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Substrate Specificity
Substances
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor Proteins
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DNA, Complementary
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Recombinant Fusion Proteins
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Protein Kinases
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Protein Serine-Threonine Kinases
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CDC2 Protein Kinase
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CDC2-CDC28 Kinases
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CDK2 protein, human
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinases
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Phosphoric Monoester Hydrolases
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CDKN3 protein, human
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Dual-Specificity Phosphatases
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Protein Tyrosine Phosphatases