Molecular regulation of receptor tyrosine kinases in hematopoietic malignancies.
Dysregulation of receptor tyrosine kinase (RTK) activity has been implicated in the progression of a variety of human leukemias. Most notably, mutations and chromosomal translocations affecting regulation of tyrosine kinase activity in the Kit receptor, the Flt3 receptor, and the PDGFbeta/FGF1 receptors have been demonstrated in mast cell leukemia, acute myeloid leukemia (AML), and chronic myelogenous leukemias (CML), respectively. In addition, critical but non-overlapping roles for the Ron and Kit receptor tyrosine kinases in the progression of animal models of erythroleukemia have been demonstrated [Persons, D., Paulson, R., Loyd, M., Herley, M., Bodner, S., Bernstein, A., Correll, P. and Ney, P., 1999. Fv2 encodes a truncated form of the Stk receptor tyrosine kinase. Nat. Gen. 23, 159-165.; Subramanian, A., Teal, H.E., Correll, P.H. and Paulson, R.F., 2005. Resistance to friend virus-induced erythroleukemia in W/Wv mice is caused by a spleen-specific defect which results in a severe reduction in target cells and a lack of Sf-Stk expression. J. Virol. 79 (23), 14586-14594.]. The various classes of RTKs implicated in the progression of leukemia have been recently reviewed [Reilly, J., 2003. Receptor tyrosine kinases in normal and malignant haematopoiesis. Blood Rev. 17 (4), 241-248.]. Here, we will discuss the mechanism by which alterations in these receptors result in transformation of hematopoietic cells, in the context of what is known about the molecular regulation of RTK activity, with a focus on our recent studies of the Ron receptor tyrosine kinase.
Correll
Pamela H
PH
Department of Veterinary and Biomedical Sciences, Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, 115 Henning Building, University Park, PA 16802-3500, United States. phc7@psu.edu
Paulson
Robert F
RF
Wei
Xin
X
D000818:Animals; D001665:Binding Sites; D019281:Dimerization; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D007942:Leukemia, Experimental / Q000473:pathology* / Q000821:virology; D008958:Models, Molecular; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D014178:Translocation, Genetic; D014443:Tyrosine / Q000737:chemistry
D014443:Tyrosine; D020794:Receptor Protein-Tyrosine Kinases