[Biological role of a neurotrophic factor fragment from pigment epithelium: structure-functional homology with a differentiation factor for the HL-60 cell line].
It was shown that the full-size neurotrophic factor from pigment epithelium (PEDF) induces the cell differentiation of the human promyelocyte leukemia cell line HL-60. A structural analysis of PEDF revealed in its C-terminal region a six-membered peptide fragment PEDF-(352-357) (PEDF-6) whose sequence is highly homologous to the 41-46 fragment of the active site of the human leukocyte differentiation factor HLDF (HLDF-6). The biological effect of PEDF and synthetic peptides PEDF-6 and HLDF-6 on the HL-60 cells and the early gastrula ectoderm of Xenopus laevis embryos was studied. On the basis of the structural and functional homologies of HLDF, PEDF, and their homologous peptides and the computer models of the spatial structures of the full-size PEDF and the PEDF with the C-terminal fragment split off tby the cleavage of the Leu380-Thr381 bond in the serpin loop, a hypothesis on the functional role of the serpin loop in PEDF was put forward.
Kostanian
I A
IA
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia. kost@ibch.ru
Zhokhov
S S
SS
Astapova
M V
MV
Dranitsyna
S M
SM
Bogachuk
A P
AP
Baĭdakova
L K
LK
Rodionov
I L
IL
Baskin
I I
II
Golubeva
O N
ON
Tombran-Tink
J
J
Lipkin
V M
VM
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D005136:Eye Proteins / Q000737:chemistry / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000737:chemistry / Q000502:physiology*; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000196:embryology; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015843:Serpins / Q000737:chemistry / Q000502:physiology*; D014982:Xenopus laevis; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D009414:Nerve Growth Factors; D011506:Proteins; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor