File Download
There are no files associated with this item.
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.1002/eji.201040313
- Scopus: eid_2-s2.0-79952108877
- PMID: 20957749
- WOS: WOS:000284059000026
- Find via
Supplementary
- Citations:
- Appears in Collections:
Article: HPK1 competes with ADAP for SLP-76 binding and via Rap1 negatively affects T-cell adhesion
Title | HPK1 competes with ADAP for SLP-76 binding and via Rap1 negatively affects T-cell adhesion |
---|---|
Authors | |
Keywords | HPK1 SLP-76 LFA-1 Rap1 ADAP |
Issue Date | 2010 |
Citation | European Journal of Immunology, 2010, v. 40, n. 11, p. 3220-3225 How to Cite? |
Abstract | The hematopoietic progenitor kinase 1 (HPK1) signals into MAPK and NFκB pathways downstream of immunoreceptors, but enigmatically is a negative regulator of leukocytes. Here, we report a novel role for HPK1 in regulating the activation of the adhesion molecule leukocyte function-associated antigen-1 (LFA-1). Upon TCR stimulation, mediated by binding of adhesion and degranulation promoting adaptor protein (ADAP) to SLP-76, a ternary complex composed of ADAP/55-kDa src kinase associated phosphoprotein (SKAP-55) and RIAM translocates to the membrane and causes membrane recruitment of the active small GTPase Ras-related protein 1 (Rap1). Active Rap1, via its binding to RapL (regulator for cell adhesion and polarization enriched in lymphoid tissues), mediates LFA-1 integrin activation. We show here that HPK1, which also binds SLP-76, compete with ADAP for SLP-76 binding. In addition, HPK1 dampens Rap1 activation, resulting in decreased LFA-1 activity. Analysis of HPK1-deficient T cells revealed increased ADAP recruitment to SLP-76 and elevated Rap1 activation in those cells, leading to increased adhesion to ICAM-1 and cell spreading. Altogether, these results describe a novel function for HPK1 in linking TCR signaling to cell adhesion regulation and provide a mechanistic explanation for the negative regulatory role of HPK1 in T-cell biology. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Persistent Identifier | http://hdl.handle.net/10722/292207 |
ISSN | 2023 Impact Factor: 4.5 2023 SCImago Journal Rankings: 1.627 |
ISI Accession Number ID |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Patzak, Irene M. | - |
dc.contributor.author | Königsberger, Sebastian | - |
dc.contributor.author | Suzuki, Akira | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Kiefer, Friedemann | - |
dc.date.accessioned | 2020-11-17T14:55:59Z | - |
dc.date.available | 2020-11-17T14:55:59Z | - |
dc.date.issued | 2010 | - |
dc.identifier.citation | European Journal of Immunology, 2010, v. 40, n. 11, p. 3220-3225 | - |
dc.identifier.issn | 0014-2980 | - |
dc.identifier.uri | http://hdl.handle.net/10722/292207 | - |
dc.description.abstract | The hematopoietic progenitor kinase 1 (HPK1) signals into MAPK and NFκB pathways downstream of immunoreceptors, but enigmatically is a negative regulator of leukocytes. Here, we report a novel role for HPK1 in regulating the activation of the adhesion molecule leukocyte function-associated antigen-1 (LFA-1). Upon TCR stimulation, mediated by binding of adhesion and degranulation promoting adaptor protein (ADAP) to SLP-76, a ternary complex composed of ADAP/55-kDa src kinase associated phosphoprotein (SKAP-55) and RIAM translocates to the membrane and causes membrane recruitment of the active small GTPase Ras-related protein 1 (Rap1). Active Rap1, via its binding to RapL (regulator for cell adhesion and polarization enriched in lymphoid tissues), mediates LFA-1 integrin activation. We show here that HPK1, which also binds SLP-76, compete with ADAP for SLP-76 binding. In addition, HPK1 dampens Rap1 activation, resulting in decreased LFA-1 activity. Analysis of HPK1-deficient T cells revealed increased ADAP recruitment to SLP-76 and elevated Rap1 activation in those cells, leading to increased adhesion to ICAM-1 and cell spreading. Altogether, these results describe a novel function for HPK1 in linking TCR signaling to cell adhesion regulation and provide a mechanistic explanation for the negative regulatory role of HPK1 in T-cell biology. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. | - |
dc.language | eng | - |
dc.relation.ispartof | European Journal of Immunology | - |
dc.subject | HPK1 | - |
dc.subject | SLP-76 | - |
dc.subject | LFA-1 | - |
dc.subject | Rap1 | - |
dc.subject | ADAP | - |
dc.title | HPK1 competes with ADAP for SLP-76 binding and via Rap1 negatively affects T-cell adhesion | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1002/eji.201040313 | - |
dc.identifier.pmid | 20957749 | - |
dc.identifier.scopus | eid_2-s2.0-79952108877 | - |
dc.identifier.volume | 40 | - |
dc.identifier.issue | 11 | - |
dc.identifier.spage | 3220 | - |
dc.identifier.epage | 3225 | - |
dc.identifier.eissn | 1521-4141 | - |
dc.identifier.isi | WOS:000284059000026 | - |
dc.identifier.issnl | 0014-2980 | - |