F
IPR043539

Grb2-like

InterPro entry
Short nameGrb2-like

Description

Growth factor receptor-bound protein 2 (Grb2) is an SH2 and SH3 domain-containing adaptor protein that links receptor tyrosine kinases to Ras signalling
[7]
. Grb2 interacts with the cytoplasmic tyrosine kinase ACK1 (activated Cdc42-associated kinase 1) and mediates its interaction with other receptor tyrosine kinases
[6]
. ACK1 is implicated in metastatic behaviour, cell spreading and migration, and epidermal growth factor receptor (EGFR) signalling
[6]
.

Human GRAP and its Drosophila homologue, downstream of receptor kinase (drk), have been shown to have a function in hearing
[8]
.

Src-like adapter proteins (SLAP and SLAP2) are involved in the regulation of immune cell surface expression and signaling. They negatively regulate T cell receptor signaling
[5]
and act as critical inhibitors of platelet (hem)ITAM signaling in the setting of arterial thrombosis and ischemic stroke
[1]
. They contain adjacent Src homology 3 (SH3) and Src homology 2 (SH2) domains. SLAP has been shown to regulate receptor tyrosine kinase (RTK) signaling
[2]
. It also binds to the receptor tyrosine kinase Flt3 and plays a role in signal transduction downstream of Flt3
[3]
. SLAP2 acts as a negative regulator of FLT3 signaling
[4]
.

This entry includes a group of adapter proteins including Grb2, GRAP, GRAPL and SLAP/SLAP2 from humans. This entry also includes Sem-5 from Caenorhabditis elegans. Sem-5 is an adapter protein which modulates signaling mediated by several receptor tyrosine kinases such as egl-15 and let-23 probably acting upstream of let-60/ras
[9, 10]
.

References

1.SLAP/SLAP2 prevent excessive platelet (hem)ITAM signaling in thrombosis and ischemic stroke in mice. Cherpokova D, Bender M, Morowski M, Kraft P, Schuhmann MK, Akbar SM, Sultan CS, Hughes CE, Kleinschnitz C, Stoll G, Dragone LL, Watson SP, Tomlinson MG, Nieswandt B. Blood 125, 185-94, (2015). View articlePMID: 25301707

2.RTK SLAP down: the emerging role of Src-like adaptor protein as a key player in receptor tyrosine kinase signaling. Wybenga-Groot LE, McGlade CJ. Cell. Signal. 27, 267-74, (2015). View articlePMID: 25446260

3.Src-Like adaptor protein (SLAP) binds to the receptor tyrosine kinase Flt3 and modulates receptor stability and downstream signaling. Kazi JU, Ronnstrand L. PLoS ONE 7, e53509, (2012). View articlePMID: 23300935

4.Src-like adaptor protein 2 (SLAP2) binds to and inhibits FLT3 signaling. Moharram SA, Chougule RA, Su X, Li T, Sun J, Zhao H, Ronnstrand L, Kazi JU. Oncotarget 7, 57770-57782, (2016). View articlePMID: 27458164

5.A novel Src homology 2 domain-containing molecule, Src-like adapter protein-2 (SLAP-2), which negatively regulates T cell receptor signaling. Pandey A, Ibarrola N, Kratchmarova I, Fernandez MM, Constantinescu SN, Ohara O, Sawasdikosol S, Lodish HF, Mann M. J. Biol. Chem. 277, 19131-8, (2002). View articlePMID: 11891219

6.Cytoplasmic ACK1 interaction with multiple receptor tyrosine kinases is mediated by Grb2: an analysis of ACK1 effects on Axl signaling. Pao-Chun L, Chan PM, Chan W, Manser E. J. Biol. Chem. 284, 34954-63, (2009). View articlePMID: 19815557

7.The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Lowenstein EJ, Daly RJ, Batzer AG, Li W, Margolis B, Lammers R, Ullrich A, Skolnik EY, Bar-Sagi D, Schlessinger J. Cell 70, 431-42, (1992). View articlePMID: 1322798

8.Dysfunction of GRAP, encoding the GRB2-related adaptor protein, is linked to sensorineural hearing loss. Li C, Bademci G, Subasioglu A, Diaz-Horta O, Zhu Y, Liu J, Mitchell TG, Abad C, Seyhan S, Duman D, Cengiz FB, Tokgoz-Yilmaz S, Blanton SH, Farooq A, Walz K, Zhai RG, Tekin M. Proc. Natl. Acad. Sci. U.S.A. 116, 1347-1352, (2019). PMID: 30610177

9.C. elegans cell-signalling gene sem-5 encodes a protein with SH2 and SH3 domains. Clark SG, Stern MJ, Horvitz HR. Nature 356, 340-4, (1992). View articlePMID: 1372395

10.The adaptor protein soc-1/Gab1 modifies growth factor receptor output in Caenorhabditis elegans. Hopper NA. Genetics 173, 163-75, (2006). View articlePMID: 16547100

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