THE CSK-LIKE PROTEINS LSK, HYL, AND MATK REPRESENT THE SAME CSK HOMOLOGOUS KINASE (CHK) AND ARE REGULATED BY STEM-CELL FACTOR IN THE MEGAKARYOBLASTIC CELL-LINE MO7E

Recently, the cDNAs for Lsk, Matk and Hyl, three Csk-related protein t yrosine kinases, have been cloned, We have examined the relationship o f Lsk, Matk and Hyl, and found that the gene for each of these protein s is localized to the same region of human chromosome 19, Further, the proteins encoded by Lsk and Matk cDNAs are immunologically similar, T hese data strongly suggest that Lsk, Hyl and Matk are the same gene pr oduct, Previous reports demonstrating expression of Hyl and Matk in he matopoietic lineages led us to investigate the regulation of Lsk expre ssion in response to stem cell factor (SCF) and granulocyte-macrophage colony stimulating factor (GIC I-CSF) in M07e, a human leukemic cell Line, Induction of Lsk/Hyl/Matk protein and mRNA was observed after tr eatment with SCF but not with GM-CSF. GM-CSF and IL-3, potent mitogens , had no effect on Lsk/Hyl/Matk expression, In contrast, PR-IA induced Lsk/Hyl/Matk but did not stimulate proliferation, Therefore, inductio n of Lsk/Hyl/Matk does not correlate,vith the capacity to stimulate pr oliferation, None of the stimuli examined increased Csk protein or mRN A expression, These data demonstrate differential regulation of Csk fa mily members by cytokines and suggest a role for Lsk/Hyl/Matk in respo nses mediated by SCF and PMA, Further, our data demonstrate that, as h as been seen in blood monocytes, cytokine driven translational control of Lsk/Hyl/Matk is likely a critical mode of regulation, Lastly, sinc e our studies strongly suggest that the Lsk, Hyl and Matk kinases are related and regulated distinctly from Csk, me and several of the origi nal authors have agreed to rename this kinase the Csk homologous kinas e (Chk).