GRB2

Last updated • 2 min readFrom Wikipedia, The Free Encyclopedia

GRB2
Grb2.JPG
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases GRB2 , ASH, EGFRBP-Grb3-3, MST084, MSTP084, NCKAP2, growth factor receptor bound protein 2
External IDs OMIM: 108355 MGI: 95805 HomoloGene: 1576 GeneCards: GRB2
Orthologs
SpeciesHumanMouse
Entrez

2885

14784

Ensembl

ENSG00000177885

ENSMUSG00000059923

UniProt

P62993

Q60631

RefSeq (mRNA)

NM_203506
NM_002086

NM_008163
NM_001313936
NM_001313937

RefSeq (protein)

NP_002077
NP_987102

NP_001300865
NP_001300866
NP_032189

Location (UCSC) Chr 17: 75.32 – 75.41 Mb Chr 11: 115.53 – 115.6 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Growth factor receptor-bound protein 2, also known as Grb2, is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene. [5] [6]

The protein encoded by this gene binds receptors such as the epidermal growth factor receptor and contains one SH2 domain and two SH3 domains. Its two SH3 domains direct complex formation with proline-rich regions of other proteins, and its SH2 domain binds tyrosine phosphorylated sequences. This gene is similar to the sem-5 gene of Caenorhabditis elegans , which is involved in the signal transduction pathway. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [7]

Function and expression

Grb2 is widely expressed and is essential for multiple cellular functions. Inhibition of Grb2 function impairs developmental processes in various organisms and blocks transformation and proliferation of various cell types. It is thus not surprising that targeted gene disruption of Grb2 in mice is lethal at an early embryonic stage. Grb2 is best known for its ability to link the epidermal growth factor receptor tyrosine kinase to the activation of Ras and its downstream kinases, ERK1,2. Grb2 is composed of an SH2 domain flanked on each side by an SH3 domain. Grb2 has two closely related proteins with similar domain organizations, Gads and Grap. Gads and Grap are expressed specifically in hematopoietic cells and function in the coordination of tyrosine kinase mediated signal transduction.

Domains

The SH2 domain of Grb2 binds to phosphorylated tyrosine-containing peptides on receptors or scaffold proteins with a preference for pY-X-N-X, where X is generally a hydrophobic residue such as valine (see ).

The N-terminal SH3 domain binds to proline-rich peptides and can bind to the Ras-guanine exchange factor SOS.

The C-terminal SH3 domain binds to peptides conforming to a P-X-I/L/V/-D/N-R-X-X-K-P motif that allows it to specifically bind to proteins such as Gab-1. [8]

Interactions

Grb2 has been shown to interact with:

See also

Related Research Articles

<span class="mw-page-title-main">Epidermal growth factor receptor</span> Transmembrane protein

The epidermal growth factor receptor is a transmembrane protein that is a receptor for members of the epidermal growth factor family of extracellular protein ligands.

<span class="mw-page-title-main">Lck</span> Lymphocyte protein

Lck is a 56 kDa protein that is found inside specialized cells of the immune system called lymphocytes. The Lck is a member of Src kinase family (SFK) and is important for the activation of T-cell receptor (TCR) signaling in both naive T cells and effector T cells. The role of Lck is less prominent in the activation or in the maintenance of memory CD8 T cells in comparison to CD4 T cells. In addition, the constitutive activity of the mouse Lck homolog varies among memory T cell subsets. It seems that in mice, in the effector memory T cell (TEM) population, more than 50% of Lck is present in a constitutively active conformation, whereas less than 20% of Lck is present as active form in central memory T cells. These differences are due to differential regulation by SH2 domain–containing phosphatase-1 (Shp-1) and C-terminal Src kinase.

<span class="mw-page-title-main">Platelet-derived growth factor receptor</span> Cell surface receptors

Platelet-derived growth factor receptors (PDGF-R) are cell surface tyrosine kinase receptors for members of the platelet-derived growth factor (PDGF) family. PDGF subunits -A and -B are important factors regulating cell proliferation, cellular differentiation, cell growth, development and many diseases including cancer. There are two forms of the PDGF-R, alpha and beta each encoded by a different gene. Depending on which growth factor is bound, PDGF-R homo- or heterodimerizes.

<span class="mw-page-title-main">ZAP70</span> Protein-coding gene in the species Homo sapiens

ZAP-70 is a protein normally expressed near the surface membrane of lymphocytes. It is most prominently known to be recruited upon antigen binding to the T cell receptor (TCR), and it plays a critical role in T cell signaling.

<span class="mw-page-title-main">SOS1</span> Protein-coding gene in the species Homo sapiens

Son of sevenless homolog 1 is a protein that in humans is encoded by the SOS1 gene.

<span class="mw-page-title-main">Adapter molecule crk</span> Protein-coding gene in the species Homo sapiens

Adapter molecule crk also known as proto-oncogene c-Crk is a protein that in humans is encoded by the CRK gene.

<span class="mw-page-title-main">Lymphocyte cytosolic protein 2</span> Protein-coding gene in the species Homo sapiens

Lymphocyte cytosolic protein 2, also known as LCP2 or SLP-76, is a signal-transducing adaptor protein expressed in T cells and myeloid cells and is important in the signaling of T-cell receptors (TCRs). As an adaptor protein, SLP-76 does not have catalytic functions, primarily binding other signaling proteins to form larger signaling complexes. It is a key component of the signaling pathways of receptors with immunoreceptor tyrosine-based activation motifs (ITAMs) such as T-cell receptors, its precursors, and receptors for the Fc regions of certain antibodies. SLP-76 is expressed in T-cells and related lymphocytes like natural killer cells.

<span class="mw-page-title-main">Linker for activation of T cells</span> Protein-coding gene in the species Homo sapiens

The Linker for activation of T cells, also known as linker of activated T cells or LAT, is a protein involved in the T-cell antigen receptor signal transduction pathway which in humans is encoded by the LAT gene. Alternative splicing results in multiple transcript variants encoding different isoforms.

<span class="mw-page-title-main">GAB2</span> Protein-coding gene in the species Homo sapiens

GRB2-associated-binding protein 2 also known as GAB2 is a protein that in humans is encoded by the GAB2 gene.

<span class="mw-page-title-main">Janus kinase 2</span> Non-receptor tyrosine kinase and coding gene in humans

Janus kinase 2 is a non-receptor tyrosine kinase. It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family, the GM-CSF receptor family, the gp130 receptor family, and the single chain receptors.

<span class="mw-page-title-main">PLCG1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">CRKL</span> Protein-coding gene in the species Homo sapiens

Crk-like protein is a protein that in humans is encoded by the CRKL gene.

<span class="mw-page-title-main">RAPGEF1</span> Protein-coding gene in the species Homo sapiens

Rap guanine nucleotide exchange factor 1 is a protein that in humans is encoded by the RAPGEF1 gene.

<span class="mw-page-title-main">NCK1</span> Protein-coding gene in the species Homo sapiens

Cytoplasmic protein NCK1 is a protein that in humans is encoded by the NCK1 gene.

<span class="mw-page-title-main">INPP5D</span> Protein-coding gene in the species Homo sapiens

Src homology 2 (SH2) domain containing inositol polyphosphate 5-phosphatase 1(SHIP1) is an enzyme with phosphatase activity. SHIP1 is structured by multiple domain and is encoded by the INPP5D gene in humans. SHIP1 is expressed predominantly by hematopoietic cells but also, for example, by osteoblasts and endothelial cells. This phosphatase is important for the regulation of cellular activation. Not only catalytic but also adaptor activities of this protein are involved in this process. Its movement from the cytosol to the cytoplasmic membrane, where predominantly performs its function, is mediated by tyrosine phosphorylation of the intracellular chains of cell surface receptors that SHIP1 binds. Insufficient regulation of SHIP1 leads to different pathologies.

<span class="mw-page-title-main">PTPRA</span> Protein-coding gene in the species Homo sapiens

Receptor-type tyrosine-protein phosphatase alpha is an enzyme that in humans is encoded by the PTPRA gene.

<span class="mw-page-title-main">NCK2</span> Protein-coding gene in the species Homo sapiens

Cytoplasmic protein NCK2 is a protein that in humans is encoded by the NCK2 gene.

<span class="mw-page-title-main">GRAP</span> Protein-coding gene in humans

GRB2-related adapter protein is a protein that in humans is encoded by the GRAP gene.

A non-receptor tyrosine kinase (nRTK) is a cytosolic enzyme that is responsible for catalysing the transfer of a phosphate group from a nucleoside triphosphate donor, such as ATP, to tyrosine residues in proteins. Non-receptor tyrosine kinases are a subgroup of protein family tyrosine kinases, enzymes that can transfer the phosphate group from ATP to a tyrosine residue of a protein (phosphorylation). These enzymes regulate many cellular functions by switching on or switching off other enzymes in a cell.

Src kinase family is a family of non-receptor tyrosine kinases that includes nine members: Src, Yes, Fyn, and Fgr, forming the SrcA subfamily, Lck, Hck, Blk, and Lyn in the SrcB subfamily, and Frk in its own subfamily. Frk has homologs in invertebrates such as flies and worms, and Src homologs exist in organisms as diverse as unicellular choanoflagellates, but the SrcA and SrcB subfamilies are specific to vertebrates. Src family kinases contain six conserved domains: a N-terminal myristoylated segment, a SH2 domain, a SH3 domain, a linker region, a tyrosine kinase domain, and C-terminal tail.

References

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  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000059923 - Ensembl, May 2017
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  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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  7. ↑ "Entrez Gene: GRB2 growth factor receptor-bound protein 2".
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