title: Human platelet Galphaq deficiency is associated with decreased Galphaq gene expression in platelets but not neutrophils.
abstract: G-proteins play an important role in platelet signal transduction and regulate responses upon activation of G-protein coupled receptors (GPCR). We have previously reported a patient with impaired platelet responses associated with deficiency in platelet Galphaq. To understand the molecular basis for this defect, the cDNA sequence encoding Galphaq (1080 bp) was obtained by reverse-transcription and polymerase chain reaction of platelet RNA; the cDNA sequence showed no mutations in the patient. Platelet Galphaq mRNA levels were decreased by >50% compared to normal subjects; platelet Galphai2 mRNA levels were normal. Neutrophil calcium mobilization and elastase secretion, upon activation with several agonists, and neutrophil Galphaq mRNA and protein levels were normal. These studies demonstrate that the patient has a defect in Galphaq gene expression in platelets but not neutrophils, possibly due to defects in transcriptional regulation or mRNA stability, and suggest a hematopoietic-lineage specific defect.
authors.affiliation: Sol Sherry Thrombosis Research Center and Fels Center for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: J
authors.initials: J
authors.lastname: Gabbeta
authors.forename: V R
authors.initials: VR
authors.lastname: Vaidyula
authors.forename: D N
authors.initials: DN
authors.lastname: Dhanasekaran
authors.forename: A K
authors.initials: AK
authors.lastname: Rao
mesh_terms: D001791:Blood Platelet Disorders / Q000097:blood / Q000235:genetics*; D001792:Blood Platelets / Q000378:metabolism*; D020013:Calcium Signaling; D019070:Cell Lineage; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000096:biosynthesis; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D005786:Gene Expression Regulation; D006474:Hemorrhagic Disorders / Q000097:blood / Q000235:genetics*; D020962:Heterotrimeric GTP-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism*; D009928:Organ Specificity; D010974:Platelet Aggregation; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood; D014158:Transcription, Genetic
chemical_list: D018076:DNA, Complementary; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D019272:Leukocyte Elastase; C498015:GNAI2 protein, human; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins