Activation of the Jak3 pathway is associated with granulocytic differentiation of myeloid precursor cells

Sushil G. Rane, James K. Mangan, Arshad Amanullah, Brian C. Wong, Renu K. Vora, Dan A. Liebermann, Barbara Hoffman, Xavier Graña, E. Premkumar Reddy

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Jak3, a member of the Janus kinase family of cytoplasmic tyrosine kinases, is expressed at low levels in immature hematopoietic cells and its expression is dramatically up-regulated during the terminal differentiation of these cells. To better understand the role of Jak3 in myeloid cell development, we have investigated the role of Jak3 in myeloid cell differentiation using the 32Dcl3 cell system. Our studies show that Jak3 is a primary response gene for granulocyte colony-stimulating factor (G-CSF) and the accumulation of tyrosine phosphorylated Jak3 correlated with cell growth inhibition and terminal granulocytic differentiation in response to G-CSF. Ectopic overexpression of Jak3 in 32Dcl3 cells resulted in an acceleration of the G-CSF-induced differentiation program that was preceded by G1 cell cycle arrest, which was associated with the up-regulation of the cyclin-dependent kinase inhibitor p27Kip1 and down-regulation of Cdk2, Cdk4, Cdk6, and Cyclin E. In addition, ectopic over-expression of Jak3 appears to result in the inactivation of PKB/Akt and Stat3- mediated proliferative pathways in the presence of G-CSF. Similarly, overexpression of Jak3 in primary bone marrow cells resulted in an acceleration of granulocytic differentiation in the presence of granulocyte-macrophage colony-stimulating factor, which was associated with their growth arrest in the G1 phase of the cell cycle. Taken together, these results indicate that Jak3-mediated signals play an important role in myeloid cell differentiation.

Original languageEnglish
Pages (from-to)2753-2762
Number of pages10
JournalBlood
Volume100
Issue number8
DOIs
StatePublished - 15 Oct 2002
Externally publishedYes

Fingerprint

Dive into the research topics of 'Activation of the Jak3 pathway is associated with granulocytic differentiation of myeloid precursor cells'. Together they form a unique fingerprint.

Cite this