SRSF protein kinase 1 (SRPK1)

SRSF protein kinase 1 (SRPK1) is a specialized serine/threonine-protein kinase that specifically phosphorylates the arginine/serine-rich (RS) domains of SR family splicing factors, such as SRSF1 and SRSF2 [1, 3]. This phosphorylation is a critical regulatory step in pre-mRNA splicing, as it controls the localization of these factors from storage sites in nuclear speckles to the nucleoplasm, thereby influencing both constitutive and alternative splicing [1, 6, 16]. In several pathological conditions, including various epithelial-derived cancers and neovascular eye diseases like wet age-related macular degeneration, SRPK1 is frequently upregulated [4, 11, 15]. This overexpression promotes the production of pro-angiogenic isoforms of vascular endothelial growth factor (VEGF-A) by shifting alternative splicing toward proximal splice sites [4, 12, 14]. By favoring pro-tumorigenic and pro-angiogenic variants, SRPK1 contributes significantly to disease progression, metastasis, and resistance to chemotherapy [11, 14, 17]. Consequently, SRPK1 has emerged as an attractive therapeutic target, with small molecule inhibitors like SPHINX31 and SRPIN340 being developed to normalize splicing patterns and inhibit pathological angiogenesis [15, 16]. Beyond its role in splicing, SRPK1 also participates in cell cycle regulation and the lifecycle of certain viruses, such as hepatitis B [1, 11].

Other names

Serine/arginine-rich protein-specific kinase 1SFRS protein kinase 1SR-protein-specific kinase 1SRSK1Serine-rich protein kinase-1Serine/threonine-protein kinase SRPK1

Inhibition of SRPK1 kinase activity prevents the phosphorylation of SR-rich splicing factors, which leads to their sequestration in nuclear speckles and a subsequent shift in the alternative splicing of target genes, most notably favoring anti-angiogenic VEGF isoforms over pro-angiogenic ones [4, 15, 18].