Cloning, expression, and initial characterization of a novel cytokine-like gene family.
We report the identification and characterization of a novel cytokine-like gene family using structure-based methods to search for novel four-helix-bundle cytokines in genomics databases. There are four genes in this family, FAM3A, FAM3B, FAM3C, and FAM3D, each encoding a protein (224-235 amino acids) with a hydrophobic leader sequence. Northern analysis indicates that FAM3B is highly expressed in pancreas, FAM3D in placenta, and FAM3A and FAM3C in almost all tissues. Immunohistochemistry showed that FAM3A is expressed prominently in the vascular endothelium, particularly capillaries. We found that FAM3A and FAM3B protein were both localized to the islets of Langerhans of the endocrine pancreas. Recombinant FAM3B protein has delayed effects on beta-cell function, inhibiting basal insulin secretion from a beta-cell line in a dose-dependent manner.
Zhu
Yuan
Y
Department of Molecular Biology, GlaxoSmithKline, King of Prussia, Pennsylvania 19406, USA. yuan_zhu-1@gsk.com
Xu
Gang
G
Patel
Arun
A
McLaughlin
Megan M
MM
Silverman
Carol
C
Knecht
Kristin
K
Sweitzer
Sharon
S
Li
Xiaotong
X
McDonnell
Peter
P
Mirabile
Rosanna
R
Zimmerman
Dawn
D
Boyce
Rogely
R
Tierney
Lauren A
LA
Hu
Erding
E
Livi
George P
GP
Wolf
Bryan
B
Abdel-Meguid
Sherin S
SS
Rose
George D
GD
Aurora
Rejeev
R
Hensley
Preston
P
Briggs
Michael
M
Young
Peter R
PR
D000818:Animals; D015152:Blotting, Northern; D002874:Chromosome Mapping; D019295:Computational Biology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D005810:Multigene Family
D016207:Cytokines; D007328:Insulin