The binding of various agonists to their specific cell-surface receptors rapidly induces formation of 2
second-messenger molecules derived from phosphatidylinositol 4,5-bisphosphate, namely, diacylglycerol and inositol
1,4,5-triphosphate. The production of these second-messenger molecules is mediated by activated phosphatidyl
inositol-specific phospholipase C (PLC) enzymes.
NCBI Summary:
The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of receptor-mediated tyrosine kinase activators. For example, when activated by SRC, the encoded protein causes the Ras guanine nucleotide exchange factor RasGRP1 to translocate to the Golgi, where it activates Ras. Also, this protein has been shown to be a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase. Two transcript variants encoding different isoforms have been found for this gene.
General function
Enzyme
Comment
Cellular localization
Cytoplasmic
Comment
Ovarian function
Oogenesis
Comment
Sette C, et al 2002 reported that Tr-kit-induced resumption of the cell cycle in mouse eggs requires activation of a Src-like kinase.
Microinjection in mouse eggs of tr-kit, a truncated form of the c-kit tyrosine kinase
present in mouse spermatozoa, causes resumption of meiosis through activation of
phospholipase Cgamma1 (PLCgamma1) and Ca(2+) mobilization from intracellular
stores. The authors show that the Src-like kinase Fyn phosphorylates Tyr161 in tr-kit and that this residue is essential for tr-kit function. Fyn is localized in the cortex region
underneath the plasma membrane in mouse oocytes. Fyn associates with tr-kit and that the interaction requires Tyr161.
The interaction between tr-kit and Fyn triggers activation of the kinase as monitored
by both autophosphorylation and phosphorylation of PLCgamma1. Co-injection of
tr-kit with the SH2 domain of Fyn, or pre-treatment with a Fyn inhibitor, impairs
oocyte activation, suggesting that activation of Fyn by tr-kit also occurs in vivo.
Finally, microinjection of constitutively active Fyn triggers oocyte activation
downstream of tr-kit but still requires PLC activity. It was suggested that the mechanism by
which tr-kit triggers resumption of meiosis of mouse eggs requires a functional
interaction with Fyn and phosphorylation of PLCgamma1.