SPRY4

SPRY4

Target · Signalling antagonist

SPRY4 Sprouty RTK signalling antagonist 4 · Protein sprouty homolog 4

SPRY4 (sprouty RTK signalling antagonist 4) is a cysteine- and proline-rich member of the sprouty family that inhibits receptor-transduced MAPK signalling. It is also known as protein sprouty homolog 4, and was previously named sprouty homolog 4 (Drosophila). Browse Assay Genie's current range of SPRY4 research reagents below, or read on for the biology behind the target.

Cytoplasm and ruffle membraneMAPK pathway inhibitorLinked to hypogonadotropic hypogonadism
299 aa
Protein length
~33 kDa
Molecular weight
5q31.3
Gene locus
Sprouty family
Protein family
Target information

What is SPRY4 (sprouty RTK signalling antagonist 4)?

SPRY4 acts as a brake on receptor tyrosine kinase signalling. It suppresses the MAPK signalling pathway transduced by the insulin receptor and EGFR, yet it does not inhibit MAPK activation by a constitutively active mutant Ras. This points to action upstream of Ras, and the protein is thought to impair the formation of GTP-Ras. Consistent with this, SPRY4 inhibits Ras-independent, but not Ras-dependent, activation of RAF1.

SPRY4 also has a role outside the core MAPK cascade. It represses integrin-mediated cell spreading by inhibiting TESK1-mediated phosphorylation of cofilin, linking growth factor signalling regulation to cytoskeletal control. In cells the protein is found in the cytoplasm and at the ruffle membrane, a cell projection associated with membrane dynamics.

The human SPRY4 gene encodes a member of a family of cysteine- and proline-rich proteins and belongs to the sprouty RTK signalling antagonist family. Alternative splicing gives rise to multiple transcript variants. Nucleotide variation in the gene has been associated with hypogonadotropic hypogonadism 17, with or without anosmia. The mouse ortholog is Spry4. Researchers studying the SPRY4 protein or gene commonly do so in the context of receptor tyrosine kinase signalling, Ras regulation and developmental disorders.

MAPK signalling research

SPRY4 inhibits receptor-transduced MAPK signalling, including pathways driven by the insulin receptor and EGFR, making it a useful node for studying pathway control.

Ras and RAF1 regulation

SPRY4 is thought to impair GTP-Ras formation and blocks Ras-independent RAF1 activation, offering a way to dissect upstream regulation.

Cytoskeleton and cell spreading

SPRY4 represses integrin-mediated cell spreading by inhibiting TESK1-mediated cofilin phosphorylation, connecting signalling to actin regulation.

Reproductive endocrine genetics

Variation in SPRY4 has been associated with hypogonadotropic hypogonadism 17 with or without anosmia, supporting genetic and disease-mechanism studies.

Background

SPRY4 frequently asked questions

What does SPRY4 do?

SPRY4 is an inhibitor of receptor-transduced MAPK signalling. It suppresses insulin receptor and EGFR-driven pathways, probably impairs formation of GTP-Ras, and inhibits Ras-independent activation of RAF1. It also represses integrin-mediated cell spreading by blocking TESK1-mediated cofilin phosphorylation.

What other names does SPRY4 have?

The HGNC name is sprouty RTK signalling antagonist 4, and UniProt calls the protein sprouty homolog 4. The previous name was sprouty homolog 4 (Drosophila). No other aliases are listed. Alternative splicing produces multiple transcript variants of the gene.

Is SPRY4 linked to disease and conserved in other species?

Nucleotide variation in SPRY4 has been associated with hypogonadotropic hypogonadism 17 with or without anosmia. The mouse ortholog is Spry4. For cross-species work, check the datasheet of any product for its validated reactivity.

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Related targets

Other sprouty family members, receptor tyrosine kinase signalling partners and cytoskeletal regulators linked to SPRY4 biology.

Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9C004; product specifications from Assay Genie datasheets.

SPRY4 Product listing