Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The X-ray crystal structure of the high affinity complex between the pleckstrin homology (PH) domain from rat phospholipase C-delta 1 (PLC-delta 1) and inositol-(1,4,5)-trisphosphate (Ins(1,4,5)P3) has been refined to 1.9 A resolution. The domain fold is similar to others of known structure. Ins(1,4,5)P3 binds on the positively charged face of the electrostatically polarized domain, interacting predominantly with the beta 1/beta 2 and beta 3/beta 4 loops. The 4- and 5-phosphate groups of Ins(1,4,5)P3 interact much more extensively than the 1-phosphate. Two amino acids in the PLC-delta 1 PH domain that contact Ins(1,4,5)P3 have counterparts in the Bruton's tyrosine kinase (Btk) PH domain, where mutational changes cause inherited agammaglobulinemia, suggesting a mechanism for loss of function in Btk mutants. Using electrostatics and varying levels of head-group specificity, PH domains may localize and orient signaling proteins, providing a general membrane targeting and regulatory function.
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PMID:Structure of the high affinity complex of inositol trisphosphate with a phospholipase C pleckstrin homology domain. 852 4

The Tec family has emerged recently as a subfamily among nonreceptor type protein-tyrosine kinases, consisting of Tec, Btk, Itk/Tsk/Emt, Bmx, and Txk/Rlk. Because many members of this family have been shown to be activated in response to growth and differentiation stimuli in hematopoietic tissues, they are presumed to function in vivo as important signaling mediators. Although that hypothesis was further strengthened by the knowledge that mutations in Btk cause agammaglobulinemia in humans, we have only limited information concerning the molecular interaction through which Tec kinases exert their effects. One characteristic feature of Tec family members is the presence of a pleckstrin homology domain in their protein structure, suggesting a physical and functional interaction with the phospholipid-dependent signaling pathways. Recent data have revealed that Tec kinases regulate phospholipase C isoforms. This review summarizes current knowledge concerning the in vivo roles of the Tec family proteins.
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PMID:The Tec family protein-tyrosine kinases: a subset of kinases for a subset of signalings. 1064 36