ARS Component B: structural characterization, tissue expression and regulation of the gene and protein (SLURP-1) associated with Mal de Meleda.
The ARS Component B gene (EMBL ID: HSARS81S, AC: X99977) encodes a 9 kD non-glycosylated polypeptide (also known as SLURP-1, SwissProt/TrEMBL: P55000), a soluble member of the human Ly6/uPAR superfamily. ARS Component B gene mutations have been implicated in Mal de Meleda. In this study we show by immunohistochemistry that SLURP-1 (secreted Ly-6/uPAR related protein, the protein product of the ARS Component B gene) is localized to human skin, exocervix, gums, stomach and esophagus. In the epidermis, keratinocytes underlying the stratum corneum are highly positive for SLURP1 immunostaining and cultured keratinocytes secrete the expected 9 kD protein. Circulating SLURP1 is detected in human plasma and urine. In the mouse, expression is evident in skin, eye, whole lung, trachea, esophagus and stomach. Human ARS Component B mRNA expression is regulated by retinoic acid, epidermal growth factor and interferon-gamma. The tissue localization and the association with Mal de Meleda suggest that ARS Component B and its protein product SLURP1 are implicated in maintaining the physiological and structural integrity of the keratinocyte layers of the skin.
Mastrangeli
Renato
R
Industria Farmaceutica Serono S.p.A Ardea site, 00040, Rome, Italy.
Donini
Silvia
S
Kelton
Christie A
CA
He
Chaomei
C
Bressan
Alessandro
A
Milazzo
Ferdinando
F
Ciolli
Veniero
V
Borrelli
Francesco
F
Martelli
Fabrizio
F
Biffoni
Mauro
M
Serlupi-Crescenzi
Ottaviano
O
Serani
Serenella
S
Micangeli
Emilia
E
El Tayar
Nabil
N
Vaccaro
Rosa
R
Renda
Tindaro
T
Lisciani
Romeo
R
Rossi
Mara
M
Papoian
Ruben
R
D000595:Amino Acid Sequence; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics*; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000378:metabolism*; D007645:Keratoderma, Palmoplantar / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D015394:Molecular Structure; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
D000950:Antigens, Ly; D012333:RNA, Messenger; C048963:SLURP1 protein, human; D014568:Urokinase-Type Plasminogen Activator