Expression of a Novel Form of the p56lck Protooncogene in Rat Cerebellar Granular Neurons

Abstract

The src family protein tyrosine kinases (PTKs) are nonreceptor kinases. Some PTKs of this family are ubiquitously expressed, whereas others have a more restricted expression, as in neurons. Lymphoid cell kinase (lck) p56lck is highly expressed in tissues of lymphoid origin and believed to be specific for hematopoietic cells. Reports suggesting that CD4 is expressed in neurons prompted us to analyze the possibility that p56lck is also expressed in these cells. By western blot and immunoprecipitations using anti‐lck antibody, an lck‐like protein was detected in lysates from primary cultures of rat cerebellar granular neurons. This 56‐kDa phosphoprotein was autophosphorylated in vitro and also phosphorylated enolase, similarly to p56lck. It was shown to be located actually in the neurons by immunocytofluorescence. Partial proteolysis mapping showed that the 56‐kDa phosphoprotein had a peptide pattern very similar to the p56lck protein. Retrotranscription‐PCR allowed the detection of an lck RNA in the neurons. The lck kinase domain was completely identical to the lymphocyte lck kinase domain, but the 5′ end was modified in the neurons. These results show that p56lck is not lymphoid specific as is widely believed; its expression in neurons might underlie the toxicity of the HIV glycoprotein gp120 to neurons.

Cell-Type-Specific Tyrosine Phosphorylation of the Herpes Simplex Virus Tegument Protein VP11/12 Encoded by Gene UL46

“…Consistent with this hypothesis, our evidence suggests that the Src family tyrosine kinase Lck, which is largely restricted to lymphocytes and some neurons (34,36,37,50), is required for the modification of VP11/12 in Jurkat T cells. Thus, tyrosine phosphorylation of VP11/12 was severely suppressed by the Src family kinase inhibitor PP2 and in the Lck-deficient Jurkat derivative JCaM 1.6.…”

“…As one approach to examining this possibility, we asked if the Src family kinase Lck (lymphocyte-specific protein tyrosine kinase) plays any role. Lck is expressed in a tissue-specific fashion, being largely restricted to lymphocytes and neurons (34,36,37,50). In T cells, Lck plays a key role in signaling through the TCR, where it phosphorylates the CD3 and TCR chains of the TCR complex in response to TCR ligation (reviewed in reference 36).…”

Sequestosome1/p62: A regulator of redox-sensitive voltage-activated potassium channels, arterial remodeling, inflammation, and neurite outgrowth

“…This nonreceptor-type Src family tyrosine kinase, mainly expressed in T lymphocytes and in neurons, plays an important role in T cell signaling [23][24][25] and neuronal functions [26,27]. SQSTM1 stably binds the SH2 domain of Lck in a phosphotyrosine-independent manner when N-terminal Ser-59 is phosphorylated by MAPK, and can subsequently compete with several other SH2 binding signal modulators [22,28].…”

“…In addition to the SQSTM1-PKCζ-K v 1.3 axis, the SQSTM1-LckDlgh1-K v 1.3-integrin signaling axis may also play a role in neurite outgrowth, since PC12 cells express Lck [140] like neurons [26,27] and T lymphocytes. Lck is involved in the regulation of neurite outgrowth in cortical neurons [141] and hippocampus neurons [142], and in the development of the retina [143].…”

Herpes Simplex Virus Requires VP11/12 To Induce Phosphorylation of the Activation Loop Tyrosine (Y394) of the Src Family Kinase Lck in T Lymphocytes

“…Although Lck conventionally is considered a lymphocyte-specific kinase, immunocytochemistry has been used to suggest that Lck also is present in mouse and rat neurons (35,56). However, the neural expression of Lck has not been widely confirmed in the literature, and the reported expression level in the mouse is 10-fold lower in brain than in the thymus (35); moreover, one report indicates that Lck cannot be detected in normal human brain (53).…”