Identification and expression of novel isoforms of human stromal cell-derived factor 1.
Stromal Cell-derived factor 1 (SDF-1) is a CXC chemokine that binds to the CXCR4 receptor. Recent publication indicates that the SDF-1/CXCR4 signaling pathway plays a pivotal role during development and in many patho-physiological conditions including hematopoiesis, blood vessel formation, cancer metastasis, angiogenesis and HIV infection. Two human SDF-1 isoforms, SDF-1alpha and SDF-1beta, have been reported to date. Here we report the identification of four additional human SDF-1 isoforms derived from alternative splicing events, SDF-1gamma, SDF-1delta, SDF-1epsilon and SDF-1phi. These SDF-1 splice variants all share the same first three exons but contain different fourth exons. The human SDF-1 gene spans over 88 kilobase-pairs on chromosome 10. Using the semi-quantitative RT-PCR method, we determined the tissue distribution of these SDF-1 isoforms. SDF-1alpha and SDF-1beta share similar expression patterns and the highest expression were detected in liver, pancreas and spleen. SDF-1gamma seems to be the human orthologue of recently isolated rat SDF-1gamma, and its expression was only detected in the heart. SDF-1delta expression can be detected in several adult tissues but the highest expression was detected in fetal liver. When transfected into HEK293 cells, all the SDF-1 isoforms can be detected as secreted proteins in the cell culture media. The conditioned media from transfected cells can stimulate cell migration in a CXCR4-dependent manner. These data suggest that the novel SDF-1 splice variants encode functional proteins.
Yu
Lan
L
Cardiovascular Division, Lilly Research Laboratories, Eli Lilly and Company, DC0434, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Cecil
Jeffrey
J
Peng
Sheng-Bin
SB
Schrementi
James
J
Kovacevic
Steven
S
Paul
Donald
D
Su
Eric Wen
EW
Wang
Jian
J
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D020029:Base Pairing; D001596:Benzylamines; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002879:Chromosomes, Human, Pair 10; D003470:Culture Media / Q000032:analysis / Q000737:chemistry; D017077:Culture Media, Conditioned / Q000494:pharmacology; D000080027:Cyclams; D004305:Dose-Response Relationship, Drug; D005091:Exons; D015870:Gene Expression / Q000502:physiology*; D014644:Genetic Variation; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000145:classification / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D001596:Benzylamines; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D003470:Culture Media; D017077:Culture Media, Conditioned; D000080027:Cyclams; D006571:Heterocyclic Compounds; D020033:Protein Isoforms; D012333:RNA, Messenger; C088327:plerixafor