描述:
Thrombopoietin (Tpo), is a key regulator of megakaryocytopoiesis and thrombopoiesis.
It is principally produced in the liver and is bound and internalized by the receptor Tpo R/
cmpl. Defects in the Tpo-Tpo R signaling pathway are associated with a variety of platelet
disorders. The 353 amino acid (aa) human Tpo precursor is cleaved to yield the 332 aa
mature protein. Mature human Tpo shares approximately 70% aa sequence homology with
mouse and rat Tpo. It is an 80 85 kDa protein that consists of an N-terminal domain with
homology to Erythropoietin (Epo) and a Cterminal domain that contains multiple Nlinked
and Olinked glycosylation sites. Tissue specific alternate splicing of human Tpo generates
multiple isoforms with internal deletions, insertions, and/or C-terminal substitutions. Tpo
promotes the differentiation, proliferation, and maturation of MK and their progenitors.
Several other cytokines can promote these functions as well but only in cooperation with Tpo.
Notably, IL3 independently induces MK development, although its effects are restricted to
early in the MK lineage. Tpo additionally promotes platelet production, aggregation, ECM
adhesion, and activation. It is cleaved by plateletderived thrombin following Arg191 within
the C-terminal domain and subsequently at other sites upon extended digestion. Full length
Tpo and shorter forms circulate in the plasma.The C terminal domain is not required for
binding to Tpo R or inducing MK growth and differentiation. Aside from its hematopoietic
effects, Tpo is expressed in the brain where it promotes the apoptosis of hypoxiasensitized
neurons and inhibits neuronal differentiation by blocking NGF induced signaling.
原厂资料:
Thrombopoietin (Tpo), is a key regulator of megakaryocytopoiesis and thrombopoiesis.
It is principally produced in the liver and is bound and internalized by the receptor Tpo R/
cmpl. Defects in the Tpo-Tpo R signaling pathway are associated with a variety of platelet
disorders. The 353 amino acid (aa) human Tpo precursor is cleaved to yield the 332 aa
mature protein. Mature human Tpo shares approximately 70% aa sequence homology with
mouse and rat Tpo. It is an 80 85 kDa protein that consists of an N-terminal domain with
homology to Erythropoietin (Epo) and a Cterminal domain that contains multiple Nlinked
and Olinked glycosylation sites. Tissue specific alternate splicing of human Tpo generates
multiple isoforms with internal deletions, insertions, and/or C-terminal substitutions. Tpo
promotes the differentiation, proliferation, and maturation of MK and their progenitors.
Several other cytokines can promote these functions as well but only in cooperation with Tpo.
Notably, IL3 independently induces MK development, although its effects are restricted to
early in the MK lineage. Tpo additionally promotes platelet production, aggregation, ECM
adhesion, and activation. It is cleaved by plateletderived thrombin following Arg191 within
the C-terminal domain and subsequently at other sites upon extended digestion. Full length
Tpo and shorter forms circulate in the plasma.The C terminal domain is not required for
binding to Tpo R or inducing MK growth and differentiation. Aside from its hematopoietic
effects, Tpo is expressed in the brain where it promotes the apoptosis of hypoxiasensitized
neurons and inhibits neuronal differentiation by blocking NGF induced signaling.