THE HUMAN TYPE-1 INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR FROM T-LYMPHOCYTES - STRUCTURE, LOCALIZATION, AND TYROSINE PHOSPHORYLATION

Inositol 1,4,5-trisphosphate receptors (IP3R) are intracellular calciu m release channels involved in diverse signaling pathways. An IP3R is thought to play a role in mobilizing calcium required for activation o f T lymphocytes. The IP3R is a tetrameric structure comprised of four similar to 300-kDa subunits encoded by a similar to 10-kilobase mRNA. In the present study we determined the structure of the human type 1 I P3R expressed in T lymphocytes (Jurkats). The IP3R in human T cells ha d a predicted molecular mass of 308 kDa and was most similar to the no n-neuronal form of the rodent type 1 IP3R. Two putative tyrosine phosp horylation sites were identified, one near the amino terminus and one near the putative channel pore at the carboxyl terminus. During T cell activation the IP3R was tyrosine phosphorylated. A site-specific anti -IP3R antibody was used to localize the carboxyl terminus of the IP3R to the cytoplasm in T cells.