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The human PIM-1 gene product is a protein serine kinase
1Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Abstract:
The human PIM-1 gene, a homologue of murine retroviral insertion site mpim-1, is overexpressed in a subset of hematolymphoid malignancies. Deduced amino acid sequence of PIM-1 complementary DNA predicts it to be a protein kinase. In vitro transcription coupled translation of the putative 313-amino acid open reading frame yields a Mr 34,000 protein; an immune complex kinase assay of the wild-type PIM-1 and not a site-directed mutant, in which the invariant Lys67 has been changed to Arg, demonstrates autophosphorylating activity on serine residues. Thus, PIM-1 is a protein serine kinase with a possible role in neoplastic transformation.
Insights
The human PIM-1 gene, a homologue of murine retroviral insertion site mpim-1, is overexpressed in hematolymphoid malignancies. PIM-1 functions as a protein serine kinase, potentially playing a role in neoplastic transformation.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- The human PIM-1 gene is homologous to the murine retroviral insertion site mpim-1.
- PIM-1 is found to be overexpressed in certain hematolymphoid malignancies.
- The deduced amino acid sequence suggests PIM-1 encodes a protein kinase.
Purpose of the Study:
- To characterize the PIM-1 gene product.
- To investigate the enzymatic activity of PIM-1.
- To explore the potential role of PIM-1 in cancer development.
Main Methods:
- In vitro transcription coupled translation was used to produce the PIM-1 protein.
- Site-directed mutagenesis was employed to create a mutant PIM-1 (Lys67 to Arg).
- Immune complex kinase assays were performed to assess autophosphorylating activity.
Main Results:
- A Mr 34,000 protein was produced from the PIM-1 open reading frame.
- Wild-type PIM-1 demonstrated autophosphorylating activity on serine residues.
- A site-directed mutant of PIM-1 (Lys67Arg) lacked autophosphorylating activity.
Conclusions:
- PIM-1 is identified as a functional protein serine kinase.
- The kinase activity of PIM-1 is dependent on the invariant Lys67 residue.
- PIM-1 may contribute to neoplastic transformation in hematolymphoid malignancies.