Selective expression and constitutive phosphorylation of SHC proteins [corrected] in the CD34+ fraction of chronic myelogenous leukemias
| Autor: | Bonati A, Carmelo Carlo-Stella, Lunghi P, Albertini R, Pinelli S, Migliaccio E, Sammarelli G, Savoldo B, Tabilio A, Pp, Dall Aglio, Pg, Pelicci |
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| Rok vydání: | 2000 |
| Předmět: |
src Homology Domains
Adaptor Proteins Vesicular Transport Src Homology 2 Domain-Containing Transforming Protein 1 Shc Signaling Adaptor Proteins Bone Marrow Leukemia Myelogenous Chronic BCR-ABL Positive Granulocyte Colony-Stimulating Factor Humans Proteins Antigens CD34 Phosphorylation Adaptor Proteins Signal Transducing |
| Zdroj: | Europe PubMed Central |
| ISSN: | 0008-5472 |
| Popis: | The BCR/ABL fusion protein is a constitutively active tyrosine kinase that is responsible for the pathogenesis of chronic myelogenous leukemia (CML). Clinically, CML is characterized by a chronic phase (CP) that eventually terminates into a blast crisis (BC). BC transformation is associated with accumulation of CD34+ blasts. We investigated the expression and phosphorylation of Src-homology-2 and collagen-homology domains (SHC) [corrected] proteins in subpopulations of CML primary cells. Shc polypeptides are tyrosine kinase substrates that are constitutively tyrosine-phosphorylated in continuous cell lines of CML origin. High levels of Shc expression were found in the CD34+ cells from CML-BC, CML-CP and normal bone marrow. In contrast, CD34- fractions from CML-CP and normal bone marrow expressed low levels of p46Shc. Shc proteins were constitutively phosphorylated in the CD34+ fractions from CML cells (both CP and BC), but not in normal CD34+ cells. These data bear implications for the role of Shc in normal hemopoiesis and CML leukemogenesis: (a) dramatic changes of Shc expression during terminal differentiation of hemopoietic cells adds a further level of regulation to the signal transduction function of Shc; and (b) constitutive Shc tyrosine-phosphorylation in the rare CD34+ cells of CML-CP might contribute to the selection of this subpopulation during the blast crisis transformation of CMLs. |
| Databáze: | OpenAIRE |
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