Ca2+ influx and protein scaffolding via TRPC3 sustain PKCbeta and ERK activation in B cells

J Cell Sci. 2010 Mar 15;123(Pt 6):927-38. doi: 10.1242/jcs.061051. Epub 2010 Feb 23.


Ca(2+) signaling mediated by phospholipase C that produces inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] and diacylglycerol (DAG) controls lymphocyte activation. In contrast to store-operated Ca(2+) entry activated by Ins(1,4,5)P(3)-induced Ca(2+) release from endoplasmic reticulum, the importance of DAG-activated Ca(2+) entry remains elusive. Here, we describe the physiological role of DAG-activated Ca(2+) entry channels in B-cell receptor (BCR) signaling. In avian DT40 B cells, deficiency of transient receptor potential TRPC3 at the plasma membrane (PM) impaired DAG-activated cation currents and, upon BCR stimulation, the sustained translocation to the PM of protein kinase Cbeta (PKCbeta) that activated extracellular signal-regulated kinase (ERK). Notably, TRPC3 showed direct association with PKCbeta that maintained localization of PKCbeta at the PM. Thus, TRPC3 functions as both a Ca(2+)-permeable channel and a protein scaffold at the PM for downstream PKCbeta activation in B cells.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / enzymology*
  • Calcium Channels / metabolism
  • Calcium Signaling*
  • Cell Line
  • Cell Membrane / enzymology
  • Chickens
  • Diglycerides / metabolism
  • Enzyme Activation
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • HeLa Cells
  • Humans
  • Ion Channel Gating
  • Mice
  • Models, Biological
  • NFATC Transcription Factors / metabolism
  • Protein Binding
  • Protein Kinase C / metabolism*
  • Protein Kinase C beta
  • Protein Transport
  • Receptors, Antigen, B-Cell / metabolism
  • TRPC Cation Channels / metabolism*


  • 1,2-diacylglycerol
  • Calcium Channels
  • Diglycerides
  • NFATC Transcription Factors
  • Receptors, Antigen, B-Cell
  • TRPC Cation Channels
  • TRPC3 cation channel
  • Protein Kinase C
  • Protein Kinase C beta
  • Extracellular Signal-Regulated MAP Kinases