TY - JOUR
T1 - Cloning and characterization of novel CIS family genes
AU - Masuhara, Masaaki
AU - Sakamoto, Hiroshi
AU - Matsumoto, Akira
AU - Suzuki, Ritsu
AU - Yasukawa, Hideo
AU - Mitsui, Kaoru
AU - Wakioka, Toru
AU - Tanimura, Shyu
AU - Sasaki, Atsuo
AU - Misawa, Hiroyuki
AU - Yokouchi, Masahiro
AU - Ohtsubo, Motoaki
AU - Yoshimura, Akihiko
N1 - Funding Information:
The ®rst three authors contributed equally to this work. We thank Ms. H. Ohgusu for excellent technical assistance, Dr. H. Wakao for STAT5 cDNA, Dr. R. Fukunaga for the JAK2 cDNAs, Dr. T. Hirano for STAT3 cDNA and M1 cells, Dr. T. Miyazaki for c-fos reporter gene, Dr. T. Fujita for technical supports, Dr. D. Hilton for showing his manuscript before publication, Dr. W. Leonard for critically reading the manuscript. Part of this work was supported by grants from the Ministry of Science, Education and Culture of Japan, the Kato Memorial Foundation, the Kowa Life Science Foundation, the Motida Memorial Science Foundation, and the Naito Memorial Foundation. M.O. is supported by Leukemia Society Ameria.
PY - 1997/10/20
Y1 - 1997/10/20
N2 - We have reported two JAK-signaling modulators, CIS (cytokine-inducible SH2 protein) and JAB (JAK2 binding protein), which are structurally related. Here we cloned three additional CIS family genes (CIS2, CIS3, and CIS4) on the basis of an expression sequence tag (EST) database search. We also found at least two additional candidates of this gene family in the database. These genes were induced by erythropoietin and granulocyte-macrophage colony stimulating factor in certain hematopoietic cell lines. The SH2 domain and a C-terminal 40 amino acid region, designated the CIS homology domain (CH domain), are highly conserved in this family, while the N-terminal regions of these proteins share little similarity. A yeast two-hybrid assay and in vitro and in vivo binding assays revealed that in addition to JAB, CIS3 bound to the JAK2 tyrosine kinase domain (JH1), although the interaction of CIS3 with the JAK2-JH1 domain was much weaker than that of JAB. Transient expression of JAB and CIS3, but not other CISs, strongly inhibited leukemia inhibitory factor (LIF)-induced STAT3-reporter gene activation in 293 cells. Furthermore, constitutive overexpression of JAB and CIS3 in M1 leukemia cells prevented LIF-induced differentiation and growth arrest. Although the physiological function remains to be investigated, CIS family genes could play a role in the negative regulation of cytokine signaling by interacting with specific targets.
AB - We have reported two JAK-signaling modulators, CIS (cytokine-inducible SH2 protein) and JAB (JAK2 binding protein), which are structurally related. Here we cloned three additional CIS family genes (CIS2, CIS3, and CIS4) on the basis of an expression sequence tag (EST) database search. We also found at least two additional candidates of this gene family in the database. These genes were induced by erythropoietin and granulocyte-macrophage colony stimulating factor in certain hematopoietic cell lines. The SH2 domain and a C-terminal 40 amino acid region, designated the CIS homology domain (CH domain), are highly conserved in this family, while the N-terminal regions of these proteins share little similarity. A yeast two-hybrid assay and in vitro and in vivo binding assays revealed that in addition to JAB, CIS3 bound to the JAK2 tyrosine kinase domain (JH1), although the interaction of CIS3 with the JAK2-JH1 domain was much weaker than that of JAB. Transient expression of JAB and CIS3, but not other CISs, strongly inhibited leukemia inhibitory factor (LIF)-induced STAT3-reporter gene activation in 293 cells. Furthermore, constitutive overexpression of JAB and CIS3 in M1 leukemia cells prevented LIF-induced differentiation and growth arrest. Although the physiological function remains to be investigated, CIS family genes could play a role in the negative regulation of cytokine signaling by interacting with specific targets.
KW - CIS
KW - Cytokine
KW - JAB
KW - JAK
KW - SH2
KW - STAT
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U2 - 10.1006/bbrc.1997.7484
DO - 10.1006/bbrc.1997.7484
M3 - Article
C2 - 9344848
AN - SCOPUS:0031581086
VL - 239
SP - 439
EP - 446
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -