Hematopoietic Progenitor Kinase 1 Associates Physically and Functionally with the Adaptor Proteins B Cell Linker Protein and SLP-76 in Lymphocytes Export

@article{citeulike:6032105, abstract = {10.1074/jbc.M106811200 B cell linker protein (BLNK) is a SLP-76-related adaptor protein essential for signal transduction from the BCR. To identify components of BLNK-associated signaling pathways, we performed a phosphorylation-dependent yeast two-hybrid analysis using BLNK probes. Here we report that the serine/threonine kinase hematopoietic progenitor kinase 1 (HPK1), which is activated upon antigen-receptor stimulation and which has been implicated in the regulation of MAP kinase pathways, interacts physically and functionally with BLNK in B cells and with SLP-76 in T cells. This interaction requires Tyr of HPK1 and the Src homology 2 (SH2) domain of BLNK/SLP-76. Via homology modeling, we defined a consensus binding site within ligands for SLP family SH2 domains. We further demonstrate that the SH2 domain of SLP-76 participates in the regulation of AP-1 and NFAT activation in response to T cell receptor (TCR) stimulation and that HPK1 inhibits AP-1 activation in a manner partially dependent on its interaction with SLP-76. Our data are consistent with a model in which full activation of HPK1 requires its own phosphorylation on tyrosine and subsequent interaction with adaptors of the SLP family, providing a mechanistic basis for the integration of this kinase into antigen receptor signaling cascades.}, author = {Sauer, Karsten and Liou, Jen and Singh, Suresh B. and Yablonski, Deborah and Weiss, Arthur and Perlmutter, Roger M.}, citeulike-article-id = {6032105}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M106811200}, citeulike-linkout-1 = {http://www.jbc.org/content/276/48/45207.abstract}, citeulike-linkout-2 = {http://www.jbc.org/content/276/48/45207.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/11487585}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=11487585}, day = {30}, doi = {10.1074/jbc.M106811200}, journal = {Journal of Biological Chemistry}, keywords = {blnk, hpk1, slp-76}, month = {November}, number = {48}, pages = {45207--45216}, posted-at = {2009-10-29 13:23:49}, priority = {2}, title = {Hematopoietic Progenitor Kinase 1 Associates Physically and Functionally with the Adaptor Proteins B Cell Linker Protein and SLP-76 in Lymphocytes}, url = {http://dx.doi.org/10.1074/jbc.M106811200}, volume = {276}, year = {2001} }

TY - JOUR ID - citeulike:6032105 L3 - citeulike-article-id:6032105 N2 - 10.1074/jbc.M106811200 B cell linker protein (BLNK) is a SLP-76-related adaptor protein essential for signal transduction from the BCR. To identify components of BLNK-associated signaling pathways, we performed a phosphorylation-dependent yeast two-hybrid analysis using BLNK probes. Here we report that the serine/threonine kinase hematopoietic progenitor kinase 1 (HPK1), which is activated upon antigen-receptor stimulation and which has been implicated in the regulation of MAP kinase pathways, interacts physically and functionally with BLNK in B cells and with SLP-76 in T cells. This interaction requires Tyr of HPK1 and the Src homology 2 (SH2) domain of BLNK/SLP-76. Via homology modeling, we defined a consensus binding site within ligands for SLP family SH2 domains. We further demonstrate that the SH2 domain of SLP-76 participates in the regulation of AP-1 and NFAT activation in response to T cell receptor (TCR) stimulation and that HPK1 inhibits AP-1 activation in a manner partially dependent on its interaction with SLP-76. Our data are consistent with a model in which full activation of HPK1 requires its own phosphorylation on tyrosine and subsequent interaction with adaptors of the SLP family, providing a mechanistic basis for the integration of this kinase into antigen receptor signaling cascades. IS - 48 JF - Journal of Biological Chemistry EP - 45216 TI - Hematopoietic Progenitor Kinase 1 Associates Physically and Functionally with the Adaptor Proteins B Cell Linker Protein and SLP-76 in Lymphocytes VL - 276 SP - 45207 KW - blnk KW - hpk1 KW - slp-76 AU - Sauer, Karsten AU - Liou, Jen AU - Singh, Suresh AU - Yablonski, Deborah AU - Weiss, Arthur AU - Perlmutter, Roger PY - 2001/11/30/ UR - http://dx.doi.org/10.1074/jbc.M106811200 ER -