Functional analysis of the cytoplastic domain of the human Mpl receptor for tyrosine‐phosphorylation of the signaling molecules, proliferation and differentiation

FEBS Letters

Matsumoto, Atsushi¹  Ohashi, Hideya¹  Morita, Haruhiko¹  Kato, Takashi¹  Miyazaki, Hiroshi¹  Tahara, Tomoyuki¹ 

[1] Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., 1-2-2, Souja-machi, Maebashi, Gunma 371, Japan

关键词: Mpl;    Thrombopoietin;    Proliferation;    Differentiation;    Signal transduction;   

DOI  :  10.1016/0014-5793(96)01047-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

To investigate the functional domains for signal transduction of human Mpl, we constructed a series of human c-mpl cDNAs with various deletions in the cytoplasmic domain, and then introduced each cDNA into murine IL-3-dependent myeloid leukemia FDC/P2 cells to establish stable transformants. We examined the growth and differentiation responses and tyrosine phosphorylation of the intracellular signaling proteins including Jak2, Tyk2, Stat3, Stat5, Vav, SHPTP2, Cbl, Shc and Shc-associated p145 when receptor stimulation occurred after thrombopoietin (TPO) binding. TPO stimulated cell proliferation and induced the expression of megakaryocyte lineage-specific AP-51 and CD61 cell surface antigens and tyrosine phosphorylation of the signaling proteins in transformants expressing full length human Mpl. These results suggested that Mpl not only induced proliferation but also transduced megakaryocyte-specific differentiation signals into FDC/P2 cells. Mutational analysis of human Mpl indicated that the N-terminal region of its cytoplasmic domain is necessary and sufficient to transduce proliferation and differentiation signals into cells, while the C-terminal region may also play important roles in transducing the differentiation signals.

【 授权许可】

Unknown