Role of the tyrosine phosphatase SHP-1 in K562 cell differentiation.
The erythro-megakaryoblastic leukemia cell line K562 undergoes erythroid or myeloid differentiation in response to treatment with various inducing agents. We observed that expression of the SH2-containing protein tyrosine phosphatase SHP-1 was induced upon exposure of K562 cells to differentiating agents. Under the same conditions, expression of SHP-2, a close relative of SHP-1, and the more distantly related PTP-1 B remained unchanged. Induction of SHP-1 expression correlates with dephosphorylation of a specific and limited set of tyrosyl phosphoproteins, suggesting that dephosphorylation of these proteins may be important for the differentiation process. Importantly, expression of exogenous SHP-1 inhibits K562 proliferation and alters the adhesion properties of these cells, indicating a more differentiated phenotype. Moreover, SHP-1 is found in a complex with both p210 Bcr-Abl and p190 Bcr-Abl, suggesting that it may regulate Bcr-Abl or Bcr-Abl-associated phosphotyrosyl proteins. Our results indicate that induction of SHP-1 expression is important for K562 differentiation in response to various inducers and raise the possibility that functional inactivation of SHP-1 may play a role in progression to blast crisis in chronic myelogenous leukemia.
Bruecher-Encke
B
B
Department of Medicine, Beth Israel-Deaconess Medical Center, Boston, MA, USA.
Griffin
J D
JD
Neel
B G
BG
Lorenz
U
U
D002448:Cell Adhesion; D002454:Cell Differentiation; D002455:Cell Division; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology; D010641:Phenotype; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000502:physiology*; D018909:src Homology Domains
D047908:Intracellular Signaling Peptides and Proteins; D016044:Fusion Proteins, bcr-abl; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases