STK-1, the Human Homolog of Flk-2/Flt-3, is Selectively Expressed in CD34+ Human Bone Marrow Cells and is Involved in the Proliferation of Early Progenitor/stem Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1994 Jan 18

PMID 7507245

Citations 87

Authors

D Small

M Levenstein

E Kim

C Carow

S Amin

P Rockwell

L Witte

C Burrow

M Z Ratajczak

A M Gewirtz

Affiliations

Soon will be listed here.

Abstract

We cloned the cDNA for stem cell tyrosine kinase 1 (STK-1), the human homolog of murine Flk-2/Flt-3, from a CD34+ hematopoietic stem cell-enriched library and investigated its expression in subsets of normal human bone marrow. The cDNA encodes a protein of 993 aa with 85% identity and 92% similarity to Flk-2/Flt-3. STK-1 is a member of the type III receptor tyrosine kinase family that includes KIT (steel factor receptor), FMS (colony-stimulating factor 1R), and platelet-derived growth factor receptor. STK-1 expression in human blood and marrow is restricted to CD34+ cells, a population greatly enriched for stem/progenitor cells. Anti-STK-1 antiserum recognizes polypeptides of 160 and 130 kDa in several STK-1-expressing cell lines and in 3T3 cells transfected with a STK-1 expression vector. Antisense oligonucleotides directed against STK-1 sequences inhibited hematopoietic colony formation, most strongly in long-term bone marrow cultures. These data suggest that STK-1 may function as a growth factor receptor on hematopoietic stem and/or progenitor cells.

Citing Articles

A Minimal PBPK/PD Model with Expansion-Enhanced Target-Mediated Drug Disposition to Support a First-in-Human Clinical Study Design for a FLT3L-Fc Molecule.

Hosseini I, Fleisher B, Getz J, Decalf J, Kwong M, Ovacik M Pharmaceutics. 2024; 16(5).

PMID: 38794321 PMC: 11125320. DOI: 10.3390/pharmaceutics16050660.

Rare variant associations with plasma protein levels in the UK Biobank.

Dhindsa R, Burren O, Sun B, Prins B, Matelska D, Wheeler E Nature. 2023; 622(7982):339-347.

PMID: 37794183 PMC: 10567546. DOI: 10.1038/s41586-023-06547-x.

Characteristics and Outcome of FLT3-ITD-Positive Pediatric Acute Myeloid Leukemia-Experience of Polish Pediatric Leukemia and Lymphoma Study Group from 2005 to 2022.

Czogala M, Czogala W, Pawinska-Wasikowska K, Ksiazek T, Bukowska-Strakova K, Sikorska-Fic B Cancers (Basel). 2023; 15(18).

PMID: 37760526 PMC: 10526903. DOI: 10.3390/cancers15184557.

French Retrospective Database Analysis of Patient Characteristics and Treatment Patterns in Patients with R/R FLT3-Mutated AML: A Registry-Based Cohort Study.

Garnham A, Bruon F, Berthon C, Lebon D, Parimi M, Polya R Oncol Ther. 2023; 11(3):375-389.

PMID: 37578642 PMC: 10447689. DOI: 10.1007/s40487-023-00239-2.

Therapeutic Targeting of FLT3 in Acute Myeloid Leukemia: Current Status and Novel Approaches.

Tecik M, Adan A Onco Targets Ther. 2022; 15:1449-1478.

PMID: 36474506 PMC: 9719701. DOI: 10.2147/OTT.S384293.

References

Kozak M . Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell. 1986; 44(2):283-92. DOI: 10.1016/0092-8674(86)90762-2. View

Hanks S, Quinn A . Protein kinase catalytic domain sequence database: identification of conserved features of primary structure and classification of family members. Methods Enzymol. 1991; 200:38-62. DOI: 10.1016/0076-6879(91)00126-h. View

Hunter T . Protein kinase classification. Methods Enzymol. 1991; 200:3-37. DOI: 10.1016/0076-6879(91)00125-g. View

Rosnet O, Marchetto S, Delapeyriere O, Birnbaum D . Murine Flt3, a gene encoding a novel tyrosine kinase receptor of the PDGFR/CSF1R family. Oncogene. 1991; 6(9):1641-50. View

Jain R, Gomer R, Murtagh Jr J . Increasing specificity from the PCR-RACE technique. Biotechniques. 1992; 12(1):58-9. View

Ratajczak M, Luger S, DeRiel K, Abrahm J, Calabretta B, Gewirtz A . Role of the KIT protooncogene in normal and malignant human hematopoiesis. Proc Natl Acad Sci U S A. 1992; 89(5):1710-4. PMC: 48522. DOI: 10.1073/pnas.89.5.1710. View

Ratajczak M, Hijiya N, Catani L, DeRiel K, Luger S, McGlave P . Acute- and chronic-phase chronic myelogenous leukemia colony-forming units are highly sensitive to the growth inhibitory effects of c-myb antisense oligodeoxynucleotides. Blood. 1992; 79(8):1956-61. View

Birg F, Courcoul M, Rosnet O, Bardin F, Pebusque M, Marchetto S . Expression of the FMS/KIT-like gene FLT3 in human acute leukemias of the myeloid and lymphoid lineages. Blood. 1992; 80(10):2584-93. View

Williams M, Quesenberry P . Hematopoietic growth factors. Hematol Pathol. 1992; 6(3):105-24. View

10.

Dexter M, Allen T . Haematopoiesis. Multi-talented stem cells?. Nature. 1992; 360(6406):709-10. DOI: 10.1038/360709a0. View

11.

Lyman S, James L, Zappone J, Sleath P, Beckmann M, Bird T . Characterization of the protein encoded by the flt3 (flk2) receptor-like tyrosine kinase gene. Oncogene. 1993; 8(4):815-22. View

12.

Maroc N, Rottapel R, Rosnet O, Marchetto S, Lavezzi C, Mannoni P . Biochemical characterization and analysis of the transforming potential of the FLT3/FLK2 receptor tyrosine kinase. Oncogene. 1993; 8(4):909-18. View

13.

Southern E . Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975; 98(3):503-17. DOI: 10.1016/s0022-2836(75)80083-0. View

14.

SANGER F, Nicklen S, Coulson A . DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977; 74(12):5463-7. PMC: 431765. DOI: 10.1073/pnas.74.12.5463. View

15.

Till J, McCulloch E . Hemopoietic stem cell differentiation. Biochim Biophys Acta. 1980; 605(4):431-59. DOI: 10.1016/0304-419x(80)90009-8. View

16.

Burnette W . "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem. 1981; 112(2):195-203. DOI: 10.1016/0003-2697(81)90281-5. View

17.

von Heijne G . Patterns of amino acids near signal-sequence cleavage sites. Eur J Biochem. 1983; 133(1):17-21. DOI: 10.1111/j.1432-1033.1983.tb07424.x. View

18.

Feinberg A, Vogelstein B . A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983; 132(1):6-13. DOI: 10.1016/0003-2697(83)90418-9. View

19.

Civin C, Strauss L, Brovall C, Fackler M, Schwartz J, Shaper J . Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells. J Immunol. 1984; 133(1):157-65. View

20.

Watson M . Compilation of published signal sequences. Nucleic Acids Res. 1984; 12(13):5145-64. PMC: 318910. DOI: 10.1093/nar/12.13.5145. View