協同活化 JAK1 和 JAK2 於造血幹原母細胞中功能角色的探
討
血球生成的過程中受到很多種細胞間素的調控。其中 Janus kinase (JAK)
蛋白質在細胞間素調控血球生成扮演著重要的角色。許多的細胞間素可
以活化兩個或兩個以上的 JAKs 。這些同時活化的 JAKs 如何影響細胞
活性的作用機轉卻不清楚。先前在我們實驗室中發現 , 同時活化 JAK1
和 JAK2 會促進 tyrosine phosphorylation 的訊息傳遞 , 並且會進一步的
活化 Signal Transduction and Activators of Transcription 5 ( STAT5) ， Ak
t 和 Mitogen-Activated Protein Kinase (MAPK) 。在這個實驗，為了更進
一步證明 JAK1 和 JAK2 的協同活化作用，將其中的一個 JAK 發生 KE
突變，利用已建立好的細胞株〝 Ba/F3-JAK1KE+2 〞細胞和〝 Ba/F3-J
AK1+2KE 細胞〞觀察是否對細胞訊號傳遞過程及細胞活性發生影響。
實驗結果發現這些細胞株的 tyrosine phosphorylation 的訊息傳遞以及 S
TAT5 ， Akt 和 MAPK 的磷酸化遠比同時活化 JAK1 和 JAK2 來的低，
並且無法維持細胞增殖的能力。更進一步的，協同活化的 JAK1 和 JAK
2 可能透過與受體的結合，形成複合體來傳遞訊息。這些結果顯示 JAK
1 和 JAK2 協同活化訊息傳遞的作用以及提供細胞增殖的活性，需要正
常激素活性，當其中一個 JAK 的活性突變，則無此作用。
Synergistic Activation of JAK1 and JAK2 and Functional Ch
aracterization in Hematopoietic Progenitor Cells
Cytokines are able to induce various signaling pathways during hematopoi
esis. Janus kinases (JAKs) were found to play a very important role in som
e signaling pathways. In most cases, more than one JAK will be simultaneo
usly activated by specific cytokine. However, it is not clear that how simult
aneous activated-JAKs can affect cellular activity. Our previous results hav
e shown that phosphorylation signaling, including tyrosine phosphorylatio
n of STAT5, MAPK and Akt, can be detected in hematopoietic progenitor
cells co-transfected with JAK1 and JAK2. In present study, one of JAKs w
as replaced by JAK1 or JAK2 inactive mutants (KE). The resulted two cell
lines, Ba/F3-JAK1KE+2 and Ba/F3-JAK1+2KE, respectively, indeed prod
uce either inhibited or reduced phosphorylation profiles of STAT5, MAPK
and Akt, as well as proliferation activity of cells. Furthermore, it is indicate
d that synergistic activated—JAK1 and —JAK2 may associate with recept
ors and form complexes to pass signals to downstream components of path
way. These results show that both JAK1 and JAK2 need to be activated to
produce synergistic effect for signal transduction and cellular proliferation.
