Identification of three novel proteins (SGSM1, 2, 3) which modulate small G protein (RAP and RAB)-mediated signaling pathway.
We report a novel protein family consisting of three members, each of which contains RUN and TBC motifs and appears to be associated with small G protein-mediated signal transduction pathway. We named these proteins as small G protein signaling modulators (SGSM1/2/3). Northern blot analysis revealed that human SGSM2/3 are expressed ubiquitously in various tissues, whereas SGSM1 is expressed mainly in brain, heart, and testis. Mouse possessed the same protein family genes, and the in situ hybridization and immunohistochemical staining of tissue sections revealed that mouse Sgsm1/2/3 are expressed in the neurons of central nervous system, indicating the strong association of Sgsm family with neuronal function. Furthermore, endogenous Sgsm1 protein was localized in the trans-Golgi network of mouse Neuro2a cells by immunofluorescence microscopy. Expression of various cDNA constructs followed by immunoprecipitation assay revealed that human SGSM1/2/3 proteins are coprecipitated with RAP and RAB subfamily members of the small G protein superfamily. Based on these results, we postulated that the SGSM family members function as modulators of the small G protein RAP and RAB-mediated neuronal signal transduction and vesicular transportation pathways.
Yang
Hao
H
Department of Molecular Biology, Keio University School of Medicine, Tokyo 160-8582, Japan.
Sasaki
Takashi
T
Minoshima
Shinsei
S
Shimizu
Nobuyoshi
N
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D014162:Transfection; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D020668:rap GTP-Binding Proteins / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; C523294:SGSM1 protein, human; C523295:SGSM2 protein, human; C523296:SGSM3 protein, human; D020691:rab GTP-Binding Proteins; D020668:rap GTP-Binding Proteins