Specific interactions among transmembrane 4 superfamily (TM4SF) proteins and phosphoinositide 4-kinase

In earlier work we established that phosphoinositide 4-kinase (PI 4-kinase) may associate with transmembrane 4 superfamily (TM4SF, tetraspanin) protei ns, but critical specificity issues were not addressed. Here we demonstrate that at least five different TM4SF proteins (CD9, CD63, CD81, CD151 and A1 5/ TALLA1) can associate with a similar or identical 55 kDa type II PI 4-ki nase. These associations were specific, since we found no evidence for othe r phosphoinositide kinases (e.g. phosphoinositide 3-kinase and phosphoinosi tide-4-phosphate 5-kinase) associating with TM4SF proteins, and many other TM4SF proteins (including CD82 and CD53) did not associate with PT 4-kinase . CD63-PI 4-kinase complexes were almost entirely intracellular, and thus a re distinct from other TM4SF-PI 4-kinase complexes (e.g. involving CD9), wh ich are largely located in the plasma membrane. These results suggest that a specific subset of TM4SF proteins may recruit PI 4-kinase to specific mem brane locations, and thereby influence phosphoinositide-dependent signallin g.