| Literature References | 1. KAUSHANSKY, K.
The enigmatic megakaryocyte gradually reveals its secrets.
BIOESSAYS 21 353-360 (1999).
2. LOK, S., KAUSHANSKY, K., HOLLY, R.D., KUIJPER, J.L., LOFTON-DAY, C.E.,
OORT, P.J., GRANT, F.J., HEIPEL, M.D., BURKHEAD, S.K., KRAMER, J.M.,
BELL L.A.N., SPRECHER C.A., BLUMBERG H., JOHNSON R., PRUNKARD D.,
CHING, A.F.T., MATHEWES, S.L., BAILEY, M.C., FORSTROM, J.W., BUDDLE, M.M.,
OSBORN, S.G., EVANS, S.J., SHEPPARD, P.O., PRESNELL, S.R., O'HARA, P.J.,
HAGEN, F.S., ROTH, G.J. AND FOSTER, D.C.
Cloning and expression of murine thrombopoietin cDNA and stimulation of
platelet production in vivo.
NATURE 369 565-568 (1994).
3. ALEXANDER, W.S.
Thrombopoietin and the c-mpl receptor: insights from gene targeting.
INT.J.BIOCHEM.CELL BIOL. 31 1027-1035 (1999).
4. PARK, H., PARK, S.S., JIN, E.H., SONG, J-S., RYU, S-E., YU, M-H.
AND HONG, H.J.
Identification of functionally important residues of human thrombopoietin.
J.BIOL.CHEM. 273 256-261 (1998).
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| Documentation | Megakaryocytes are large cells found in the bone marrow that, upon
maturation, fragment into platelets. The term thrombopoietin (TPO) was
coined in 1958 to describe a possible humoral entity that stimulates
megakaryocyte development into platelets. The discovery of a novel
haemopoietic cytokine receptor encoded by the proto-oncogene c-mpl raised
speculation that this was the receptor for thrombopoietin, and prompted a
search for the endogenous ligand [1]. The ligand was cloned and in vivo-
administration of the recombinant protein to mice produced a 4-fold increase
in circulating platelets. These results suggested that the c-mpl ligand was
in fact thrombopoietin [2].
More recent studies have shown that TPO is expressed in hepatocytes, the
renal proximal tubules, muscle cells and stromal cells in haemopoietic
organs [3]. TPO is a 332-residue protein with a 2-domain structure. The
domain at the N-terminus is 153 amino acids long, shares similarity with
erythropoietin and can itself stimulate megakaryopoiesis in vitro. A four-
alpha-helical structure is predicted, which is typical of many haemopoietic
regulators. The C-terminal domain is 179 amino acids long, is highly
variable across species and is not required for the binding of c-mpl [4].
THROMBOPTN is a 6-element fingerprint that provides a signature for the
thrombopoietins. The fingerprint was derived from an initial alignment of 3
sequences: the motifs were drawn from conserved regions spanning the
N-terminal domain. Two iterations on SPTR39_15f were required to reach
convergence, at which point a true set comprising 5 sequences was identified.
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