Misshapen-like kinase 1 (MINK1)

Misshapen-like kinase 1 (MINK1) is a serine/threonine protein kinase encoded by the MINK1 gene in humans, belonging to the germinal center kinase (GCK) family and further classified as a member of the MAP4K (mitogen-activated protein kinase kinase kinase kinase) family[1][2][3]. MINK1 is structurally and functionally similar to NIK-related kinases and plays diverse roles in cellular signaling, notably activating the JNK and p38 MAP kinase pathways, and acting as a regulator of neuronal differentiation, actin cytoskeleton reorganization, cell adhesion, and migration[1][2]. It is a critical regulator of Hippo pathway signaling, impacting organ size and tumor suppression through proliferation and apoptosis control[2][3]. MINK1 has been identified as a key mediator of 5-fluorouracil resistance in oral squamous cell carcinoma, acting via AKT-mediated phosphorylation of MDM2 and subsequent p53 degradation; inhibition of MINK1 kinase activity (by lestaurtinib) sensitizes chemoresistant tumors to 5FU and limits cancer cell survival and migration[4]. Elevated MINK1 expression is associated with treatment-resistant cancer phenotypes, and its inhibition represents a promising therapeutic strategy in select malignancies[4].

Other names

B55MAP4K6MINKYSK2ZC3hMINKGCK family kinase MiNKMAPK/ERK kinase kinase kinase 6MEK kinase kinase 6MEKKK 6Misshapen/NIK-related kinase

Inhibition of MINK1 kinase activity (lestaurtinib) restores sensitivity to 5-fluorouracil (5FU) by modulating AKT/MDM2/p53 signaling, promoting apoptosis and limiting migration/proliferation of chemoresistant cancer cells