Growth hormone-dependent tyrosine phosphorylation of a GH receptor-associated high molecular WEIGHT protein immunologically related to JAK2

A critical step in growth hormone (GH) signalling is the GH-induced activat ion of the GH receptor (GHR)associated tyrosine kinase, JAK2. JAK2 is a 120 kD member of the Janus family of tyrosine kinases, whose other mammalian m embers include JAK1, JAK3, and TYK2. Using 3T3-F442A murine preadipocytes, we now report detection of a M-r similar to 170 kD protein, referred to as HMW ("high molecular weight") JAK2, that is specifically reactive in immuno precipitation and immunoblotting experiments with three independently-deriv ed anti JAK2 antibodies-two directed at carboxyl-terminal regions of the mo lecule and one directed at the amino-terminus. Like JAK2, HMW JAK2 is tyros ine phosphorylated in response to GH treatment of cells and is coimmunoprec ipitated with anti-GHR serum. Thus, HMW JAK2 is a protein not heretofore de scribed that is immunologically related to JAK2 and is physically and funct ionally associated with the GHR. (C) 1998 Academic Press.