The calponin homology domain of Vav1 associates with calmodulin and is prerequisite to T cell antigen receptor-induced calcium release in Jurkat T lymphocytes.
Vav1 is a guanine nucleotide exchange factor that is expressed specifically in hematopoietic cells and plays important roles in T cell development and activation. Vav1 consists of multiple structural domains so as to facilitate both its guanine nucleotide exchange activity and scaffold function following T cell antigen receptor (TCR) engagement. Previous studies demonstrated that the calponin homology (CH) domain of Vav1 is required for TCR-stimulated calcium mobilization and thus downstream activation of nuclear factor of activated T cells. However, it remained obscure how Vav1 functions in regulating calcium flux. In an effort to explore molecules interacting with Vav1, we found that calmodulin bound to Vav1 in a calcium-dependent and TCR activation-independent manner. The binding site was mapped to the CH domain of Vav1. Reconstitution of vav1-null Jurkat T cells (J.Vav1) with CH-deleted Vav1 exhibited a severe deficiency in calcium release to the same extent as that of Jurkat cells treated with the calmodulin inhibitor or J.Vav1 cells. The defect persisted even when phospholipase-Cgamma1 was fully activated, indicating a prerequisite role of Vav1 CH domain in calcium signaling. The results suggest that Vav1 and calmodulin function cooperatively to potentiate TCR-induced calcium release. This study unveiled a mechanism by which the Vav1 CH domain is involved in calcium signaling and provides insight into our understanding of the role of Vav1 in T cell activation.
T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T1 T20 T21 T22 T23 T24 T25 T26 T27 T28 T29 T2 T30 T31 T32 T33 T34 T35 T36 T37 T38 T39 T3 T40 T41 T42 T43 T4 T5 T6 T7 T8 T9
CHEMICAL GENE-Y GENE-Y GENE-Y GENE-N GENE-Y GENE-N GENE-Y GENE-Y GENE-N CHEMICAL GENE-N GENE-Y GENE-Y GENE-N GENE-N GENE-N GENE-Y GENE-Y GENE-N GENE-Y CHEMICAL GENE-Y GENE-Y GENE-Y GENE-N GENE-N GENE-Y GENE-Y GENE-Y GENE-N GENE-Y CHEMICAL GENE-Y GENE-N GENE-Y GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
calcium Vav1 calmodulin Vav1 guanine nucleotide exchange factor phospholipase-Cgamma1 Vav1 CH domain Vav1 calmodulin TCR guanine nucleotide Vav1 CH domain Vav1 Vav1 T cell antigen receptor TCR calponin homology (CH) domain Vav1 TCR nuclear factor of activated T cells Vav1 calcium Vav1 calmodulin Vav1 TCR CH domain Vav1 vav1 Vav1 CH Vav1 calcium Vav1 calponin homology domain calmodulin T cell antigen receptor calcium guanine nucleotide calcium calcium calcium calcium