TY - JOUR
T1 - Differently phosphorylated forms of the cortactin homolog HS1 mediate distinct functions in natural killer cells
AU - Butler, Boyd
AU - Kastendieck, Diana H.
AU - Cooper, John A.
N1 - Funding Information:
NKL cells were a gift from M. Robertson (Indiana University School of Medicine); b2 integrin and Pyk2 were gifts from S. Blystone (State University of New York, Syracuse); Vav1 was a gift from V. Tybulewicz (National Institute for Medical Research, London); and the GFP-actin expression plasmid was provided by B. Imhof (University Medical Centre, Geneva). We thank the Siteman Cancer Center High Speed Sorter Core Facility, W. Eades and J. Hughes. Supported by the US National Institutes of Health (GM 38542 to J.A.C.), the National Institute of Allergy and Infectious Diseases (71429 to B.B.) and the US National Cancer Institute (P30 CA91842 to the Siteman Cancer Center High Speed Sorter Core Facility).
PY - 2008/8
Y1 - 2008/8
N2 - Here we investigated the involvement of HS1, the hematopoietic cell-specific homolog of cortactin, in the actin-based functions of natural killer cells. Involvement of HS1 in T cell regulation has been established, as HS1 is required for the formation of immune synapses. 'Knockdown' of HS1 in natural killer cells resulted in defective lysis of target cells, cell adhesion, chemotaxis and actin assembly at the lytic synapse. Phosphorylation of the tyrosine residue at position 397 (Tyr397) was required for adhesion to the integrin ligand ICAM-1 and for cytolysis, whereas phosphorylation of Tyr378 was required for chemotaxis. Phosphorylation of Tyr397 was also required for integrin signaling and recruitment of integrins, adaptors and actin to the lytic synapse. Thus, HS1 is essential for signaling and actin assembly in natural killer cells, and the functions of the two phosphorylated tyrosine residues are distinct and separable.
AB - Here we investigated the involvement of HS1, the hematopoietic cell-specific homolog of cortactin, in the actin-based functions of natural killer cells. Involvement of HS1 in T cell regulation has been established, as HS1 is required for the formation of immune synapses. 'Knockdown' of HS1 in natural killer cells resulted in defective lysis of target cells, cell adhesion, chemotaxis and actin assembly at the lytic synapse. Phosphorylation of the tyrosine residue at position 397 (Tyr397) was required for adhesion to the integrin ligand ICAM-1 and for cytolysis, whereas phosphorylation of Tyr378 was required for chemotaxis. Phosphorylation of Tyr397 was also required for integrin signaling and recruitment of integrins, adaptors and actin to the lytic synapse. Thus, HS1 is essential for signaling and actin assembly in natural killer cells, and the functions of the two phosphorylated tyrosine residues are distinct and separable.
UR - http://www.scopus.com/inward/record.url?scp=47849111586&partnerID=8YFLogxK
U2 - 10.1038/ni.1630
DO - 10.1038/ni.1630
M3 - Article
C2 - 18587398
AN - SCOPUS:47849111586
SN - 1529-2908
VL - 9
SP - 887
EP - 897
JO - Nature immunology
JF - Nature immunology
IS - 8
ER -