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. 2019 Jun 25;10:1449. doi: 10.3389/fimmu.2019.01449

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Copyright © 2019 Gerth and Mattner.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Signaling domains of slp-76. SLP76 (SRC homology 2 (SH2)-domain-containing leukocyte protein of 76 kDa) contains inducibly phosphorylated tyrosines in the amino (N) terminus, a central proline-rich (PR-) domain and a carboxy (C)-terminal SH2 domain. The N-terminal acidic domain binds to the SH2 domains of the guanine nucleotide exchange factor Vav, the adaptor protein Nck and the Tec-family kinase Itk. The subsequent signaling pathways influence predominantly the reorganization of actin. This domain of slp-76 interacts also with the phosphatidylinositol 3-kinases (PI3K) which interfere with multiple cellular functions such as proliferation, differentiation and survival. The central proline-rich domain of slp-76 interacts with the phospholipase PLCγ-1 and the adaptor molecule GADS (Grb2-related adaptor downstream of Shc). The C-terminal SH2 domain of slp-76 binds to the serine-threonine kinase HPK-1 (hematopoietic progenitor kinase 1) and to the adhesion and degranulation-promoting adaptor protein (ADAP), two molecule associated with the formation of the immunological synapse, integrin activation/expression and inside-out and outside-in signaling cascades. ADAP, adhesion- and degranulation-promoting adaptor protein; GADS, GRB2-related adaptor protein; GRB2, growth-factor-receptor-bound protein 2; HPK1, hematopoietic progenitor kinase 1; ITK, interleukin-2-inducible T-cell kinase; Lck, lymphocyte-specific protein tyrosine kinase; NCK, non-catalytic region of tyrosine kinase; PLCγ1, phospholipase Cgamma1; PI3K, phosphatidylinositol 3-kinase; PR, proline-rich; Vav, guanine nucleotide exchange factor.