Function Research Of The Association Of PKD2 With Lck And ERK3

Protein kinase D2 (PKD2) is a member of the PKD serine/threonine protein kinase family that has been implicated in the regulation of a variety of cellular processes including proliferation, survival, protein trafficking and immune response. In the present study, we report a novel interaction between PKD2 and Lck, a member of the Src tyrosine protein kinase family predominantly expressed in T cells. The interaction involved the C-terminal kinase domains of both PKD2 and Lck. Moreover, co-expression of Lck could enhance tyrosine phosphorylation of PKD2 and increase its kinase activity. Finally, we demonstrate that PKD2 could enhance T cell receptor (TCR)-induced nuclear factor of T cells (NFAT) activity in Jurkat T cells. These results suggest that Lck regulates the activity of PKD2 by tyrosine phosphorylation, which may in turn modulate the physiological functions of PKD2 during TCR-induced T cell activation.Extracellular-regulated kinase 3(ERK3) is an atypical member of ERKs, lacking the threonine and tyrosine residues in the activation loop, carrying a unique C-terminal extension and being mainly regulated by its own protein stability. In the present study, we report a novel interaction between PKD2 and ERK3. PKD2 binds ERK3 on its NDR2 domain and protects ERK3 against ubiquitination. This association remarkably stabilizes ERK3 at protein level. In addition, the mRNA level of ERK3 was investigated in various human tumor tissues.