Fig. 8From: Prolactin-induced PAK1 tyrosyl phosphorylation promotes FAK dephosphorylation, breast cancer cell motility, invasion and metastasisProposed mechanism for the role of PRL-activated PAK1 in breast cancer cell migration. PRL binding to the PRLR results in activation of the non-receptor tyrosine kinase JAK2. JAK2 tyrosyl phosphorylates PAK1 on Y153, 201, and 285, enhancing PAK1 kinase and scaffolding activities. PRL treatment also leads to FAK auto-phosphorylation at Y397. Activated PAK1 phosphorylates MEK1 at S298, resulting in increased MEK1/ERK binding and enhanced ERK activity. Active ERK phosphorylates FAK at S910, leading to dephosphorylation of FAK at Y397 by the tyrosine phosphatase PTP-PEST as shown by Zheng et al. (2009). FAK dephosphorylation decreases FAK kinase activity and promotes adhesion turnover and breast cancer cell migrationBack to article page