An aPKC-Exocyst Complex Controls Paxillin Phosphorylation and Migration through Localised JNK1 Activation

Abstract

The exocyst/aPKC complex controls the spatiotemporal activation of the kinases JNK and ERK at the leading edge of migrating cells and thereby controls the dynamic behaviour of the adhesion protein paxillin during cell migration.

Control of MT1-MMP transport by atypical PKC during breast-cancer progression

“…In previous studies, we implicated the exocyst complex in MT1-MMP trafficking to invadopodia in MDA-MB-231 breast-tumor cells (15) and identified a coordinated function of the exocyst complex and aPKCζ/ι in migrating cells (19). MT1-MMP and aPKCι are overexpressed in various cancers, including breast cancers, and up-regulation is associated with poor prognosis (8,9,22,24).…”

“…migrating cells, so controlling paxillin phosphorylation and regulating focal adhesion dynamics (19). In addition, several lines of evidence implicate aPKCζ/ι in cancer: aPKCς is required for epidermal growth factor-induced chemotaxis of human breast-cancer cells (20), and aPKCζ/ι promotes matrix degradation by Src-transformed mouse NIH 3T3 fibroblasts (21).…”

Frequent epigenetic inactivation ofKIBRA,an upstream member of the Salvador/Warts/Hippo (SWH) tumor suppressor network, is associated with specific genetic event in B-cell acute lymphocytic leukemia

“…Human KIBRA has been reported to play a role in cell migration and is known to be phosphorylated by protein kinase C (PKC) zeta. [27][28][29] MSTs and LATs members of the SWH pathway have previously been shown to be epigenetically inactivated in certain human cancers. Frequent methylation of MST2 (96%) was found in head and neck squamous cell carcinoma and less frequently for LATS1 (24%) and LATS2 (8%).…”

PKCζ regulates Notch receptor routing and activity in a Notch signaling-dependent manner

“…Atypical protein kinase C (aPKC) may be an interesting candidate for control of Notch receptor intracellular trafficking and function, as there is an emerging view that aPKCs play a key role both in regulation of protein trafficking and in various differentiation processes. aPKCs play critical roles in cell polarization [24,25], asymmetric cell division [26,27] and migration [28][29][30], and also link cell polarity cues to differentiation [26,27,[31][32][33][34]. aPKCs are critical regulators of the organization of the apical-basal axis in epithelial cells, a process in which aPKC functions together with PAR-3 and PAR-6 in a complex, and this PAR-3/ PAR-6/aPKC complex is pivotal for establishing cellular polarity and organizing cellular junctions [35][36][37][38].…”